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alcl cell lines karpas 299  (DSMZ)


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    DSMZ alcl cell lines karpas 299
    (A) Volcano plot and (B) MA plot of circular RNA expression comparing ALK(+) <t>ALCL</t> primary biopsies (n=39) and healthy tissues (reactive lymph nodes, RLN, n=9). (C) expression of circZBTB46 (left) and ZBTB46 mRNA (right) assessed by RNA-Seq in ALK(+) ALCL primary samples versus RLN. (D) ZBTB46 mRNA expression (RMA) from microarray datasets in ALK(+) ALCL (n=61), angioimmunoblastic T-cell lymphoma (AITL, n=83) and peripheral T-cell lymphoma not otherwise specified (PTCL-NOS, n=71) primary biopsies. (E) ZBTB46 mRNA expression (log2 of the transcript count per million (lenghScaled TPM) from RNA-Seq data in five ALK(+) ALCL cell lines <t>(KARPAS-299,</t> SU-DHL-1, SUP-M2, Pio, COST), two ALK(-) ALCL cell lines (FEPD, MAC-2A) and CD3(+) lymphocytes stimulated (S, n=3) or not (NS, n=3). (F) Quantitative real-time PCR (RTLqPCR) analysis of circZBTB46 and ZBTB46 mRNAs in the same cell types. MLN51 was used as an internal control. Values are expressed as 2^(–Δ)Ct relative ratios. Experiments were performed at least in triplicate. Statistical significance was assessed via an unpaired two-tailed Student’s t test with Welch’s correction: P < 0.01 ( ** ), P < 0.001 (*** ), P < 0.0001 (**** ), ns = not significant. Data are expressed as means ± SD. (G) ZBTB46 mRNA expression across hematological malignancies in the Cancer Cell Line Encyclopedia (CCLE) dataset. (H) Representative immunohistochemical image of an ALK(+) ALCL primary tumor showing ZBTB46 (brown, arrowhead) and CD68 (red, arrow) expression. Cell nuclei were counterstained with hematoxylin (blue). Original magnification, ×24.6.
    Alcl Cell Lines Karpas 299, supplied by DSMZ, used in various techniques. Bioz Stars score: 95/100, based on 136 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/product/alcl+cell+lines/SU-DHL-1/bio_rxiv__64898__2026__01__13__699235-158-1-19
    Average 95 stars, based on 136 article reviews
    alcl cell lines karpas 299 - by Bioz Stars, 2026-09
    95/100 stars

    Images

    1) Product Images from "CircZBTB46, a promising therapeutic target in crizotinib resistant ALK-positive T lymphomas"

    Article Title: CircZBTB46, a promising therapeutic target in crizotinib resistant ALK-positive T lymphomas

    Journal: bioRxiv

    doi: 10.64898/2026.01.13.699235

    (A) Volcano plot and (B) MA plot of circular RNA expression comparing ALK(+) ALCL primary biopsies (n=39) and healthy tissues (reactive lymph nodes, RLN, n=9). (C) expression of circZBTB46 (left) and ZBTB46 mRNA (right) assessed by RNA-Seq in ALK(+) ALCL primary samples versus RLN. (D) ZBTB46 mRNA expression (RMA) from microarray datasets in ALK(+) ALCL (n=61), angioimmunoblastic T-cell lymphoma (AITL, n=83) and peripheral T-cell lymphoma not otherwise specified (PTCL-NOS, n=71) primary biopsies. (E) ZBTB46 mRNA expression (log2 of the transcript count per million (lenghScaled TPM) from RNA-Seq data in five ALK(+) ALCL cell lines (KARPAS-299, SU-DHL-1, SUP-M2, Pio, COST), two ALK(-) ALCL cell lines (FEPD, MAC-2A) and CD3(+) lymphocytes stimulated (S, n=3) or not (NS, n=3). (F) Quantitative real-time PCR (RTLqPCR) analysis of circZBTB46 and ZBTB46 mRNAs in the same cell types. MLN51 was used as an internal control. Values are expressed as 2^(–Δ)Ct relative ratios. Experiments were performed at least in triplicate. Statistical significance was assessed via an unpaired two-tailed Student’s t test with Welch’s correction: P < 0.01 ( ** ), P < 0.001 (*** ), P < 0.0001 (**** ), ns = not significant. Data are expressed as means ± SD. (G) ZBTB46 mRNA expression across hematological malignancies in the Cancer Cell Line Encyclopedia (CCLE) dataset. (H) Representative immunohistochemical image of an ALK(+) ALCL primary tumor showing ZBTB46 (brown, arrowhead) and CD68 (red, arrow) expression. Cell nuclei were counterstained with hematoxylin (blue). Original magnification, ×24.6.
    Figure Legend Snippet: (A) Volcano plot and (B) MA plot of circular RNA expression comparing ALK(+) ALCL primary biopsies (n=39) and healthy tissues (reactive lymph nodes, RLN, n=9). (C) expression of circZBTB46 (left) and ZBTB46 mRNA (right) assessed by RNA-Seq in ALK(+) ALCL primary samples versus RLN. (D) ZBTB46 mRNA expression (RMA) from microarray datasets in ALK(+) ALCL (n=61), angioimmunoblastic T-cell lymphoma (AITL, n=83) and peripheral T-cell lymphoma not otherwise specified (PTCL-NOS, n=71) primary biopsies. (E) ZBTB46 mRNA expression (log2 of the transcript count per million (lenghScaled TPM) from RNA-Seq data in five ALK(+) ALCL cell lines (KARPAS-299, SU-DHL-1, SUP-M2, Pio, COST), two ALK(-) ALCL cell lines (FEPD, MAC-2A) and CD3(+) lymphocytes stimulated (S, n=3) or not (NS, n=3). (F) Quantitative real-time PCR (RTLqPCR) analysis of circZBTB46 and ZBTB46 mRNAs in the same cell types. MLN51 was used as an internal control. Values are expressed as 2^(–Δ)Ct relative ratios. Experiments were performed at least in triplicate. Statistical significance was assessed via an unpaired two-tailed Student’s t test with Welch’s correction: P < 0.01 ( ** ), P < 0.001 (*** ), P < 0.0001 (**** ), ns = not significant. Data are expressed as means ± SD. (G) ZBTB46 mRNA expression across hematological malignancies in the Cancer Cell Line Encyclopedia (CCLE) dataset. (H) Representative immunohistochemical image of an ALK(+) ALCL primary tumor showing ZBTB46 (brown, arrowhead) and CD68 (red, arrow) expression. Cell nuclei were counterstained with hematoxylin (blue). Original magnification, ×24.6.

    Techniques Used: RNA Expression, Expressing, RNA Sequencing, Microarray, Real-time Polymerase Chain Reaction, Control, Two Tailed Test, Immunohistochemical staining

    (A) Relative expression of circZBTB46 and ZBTB46 mRNAs in COST and KARPAS-299 cells transfected for 48 h with control siRNA (siCTL) or two different circZBTB46-targeting siRNAs (siCircZBTB46#1 and #2), as measured by RTLqPCR. (B) Viability (Annexin V-Pacific Blue/PI flow cytometry) of COST and KARPAS-299 cells transfected with siCircZBTB46#1 or #2 and subsequently treated with crizotinib (3 µM, 48 h). (C) Relative expression of circZBTB46 and ZBTB46 mRNAs in COST, SUPM2 and Pio cells transduced with Cas13 and either control gRNA (CTL) or gRNA targeting circZBTB46, as assessed by RTLqPCR. (D) Viability (Annexin V-Pacific Blue/PI flow cytometry) of COST, SUPM2 and Pio cells transduced as described in (C) and treated with crizotinib (100 or 200 nM) for 7 days. ( E ) Relative expression of circZBTB46 and ZBTB46 mRNAs in crizotinib-resistant cells established from MTK PDX-derived cells transfected for 48 h with control siRNA (siCTL) or two different siRNAs targeting circZBTB46 (siCircZBTB46#1 and #2), as measured by RTLqPCR. ( F-G ) Cell viability assessed by Annexin V-Pacific Blue/PI staining (flow cytometry) in crizotinib-resistant cells established from MTK PDX-derived cells transfected with siCircZBTB46#1 or #2, without treatment ( F ) or after crizotinib exposure ( G ) (400 nM, 48 h). ( H ) Relative expression of circZBTB46 and ZBTB46 mRNAs in COST crizotinib-resistant cells (COSTR200) after lentiviral transduction with circZBTB46-targeting shRNAs, as measured by RTLqPCR. ( I ) Viability of COSTR200 cells determined by Annexin V/PI staining (flow cytometry) after transduction with circZBTB46 shRNA and subsequent treatment with crizotinib (1,000 nM, 7 days). MLN51 was used as an internal control for RTLqPCR. Expression data are displayed as 2-ΔΔCt relative values. Statistical significance was assessed via an unpaired two-tailed Student t test with Welch correction: P < 0.05 ( * ), P < 0.01 (** ), P < 0.0001 ( **** ), ns = not significant. Data are expressed as means ± SEMs.
    Figure Legend Snippet: (A) Relative expression of circZBTB46 and ZBTB46 mRNAs in COST and KARPAS-299 cells transfected for 48 h with control siRNA (siCTL) or two different circZBTB46-targeting siRNAs (siCircZBTB46#1 and #2), as measured by RTLqPCR. (B) Viability (Annexin V-Pacific Blue/PI flow cytometry) of COST and KARPAS-299 cells transfected with siCircZBTB46#1 or #2 and subsequently treated with crizotinib (3 µM, 48 h). (C) Relative expression of circZBTB46 and ZBTB46 mRNAs in COST, SUPM2 and Pio cells transduced with Cas13 and either control gRNA (CTL) or gRNA targeting circZBTB46, as assessed by RTLqPCR. (D) Viability (Annexin V-Pacific Blue/PI flow cytometry) of COST, SUPM2 and Pio cells transduced as described in (C) and treated with crizotinib (100 or 200 nM) for 7 days. ( E ) Relative expression of circZBTB46 and ZBTB46 mRNAs in crizotinib-resistant cells established from MTK PDX-derived cells transfected for 48 h with control siRNA (siCTL) or two different siRNAs targeting circZBTB46 (siCircZBTB46#1 and #2), as measured by RTLqPCR. ( F-G ) Cell viability assessed by Annexin V-Pacific Blue/PI staining (flow cytometry) in crizotinib-resistant cells established from MTK PDX-derived cells transfected with siCircZBTB46#1 or #2, without treatment ( F ) or after crizotinib exposure ( G ) (400 nM, 48 h). ( H ) Relative expression of circZBTB46 and ZBTB46 mRNAs in COST crizotinib-resistant cells (COSTR200) after lentiviral transduction with circZBTB46-targeting shRNAs, as measured by RTLqPCR. ( I ) Viability of COSTR200 cells determined by Annexin V/PI staining (flow cytometry) after transduction with circZBTB46 shRNA and subsequent treatment with crizotinib (1,000 nM, 7 days). MLN51 was used as an internal control for RTLqPCR. Expression data are displayed as 2-ΔΔCt relative values. Statistical significance was assessed via an unpaired two-tailed Student t test with Welch correction: P < 0.05 ( * ), P < 0.01 (** ), P < 0.0001 ( **** ), ns = not significant. Data are expressed as means ± SEMs.

    Techniques Used: Expressing, Transfection, Control, Flow Cytometry, Transduction, Derivative Assay, Staining, shRNA, Two Tailed Test

    circZBTB46 modulates PIP5K1C by sponging miR-25. (A) Volcano plot showing differentially expressed genes in crizotinib-resistant cells established from MTK PDX-derived cells transfected with control siRNA (siCTL) or siRNAs targeting circZBTB46 (siCircZBTB46#1 and #2). (B) Expression of PIP5K1C at the mRNA (top panel, RTLqPCR) and protein (bottom panel, Western blot) levels in COST, MTK-PDX and COSTR200 ALK(+) ALCL cells after circZBTB46 siRNA transfection (48 h). (C) Expression of PIP5K1C at the mRNA (left panel) and protein (right panel) levels in stable COSTR200 cells expressing either control shRNA (CTL) or shRNA targeting circZBTB46, as assessed by RTLqPCR and Western blot, respectively. (D) Expression of PIP5K1C in Pio ALK(+) ALCL cells stably expressing Cas13 with control gRNA (CTL) or gRNA targeting circZBTB46, as determined by RTLqPCR (left panel) and immunoblotting (right panel), respectively. (E) RNA enrichment after RNA pull-down using biotinylated probes targeting circZBTB46 or control probes . (F) Volcano plot showing in the COST cell line differentially enriched RNAs in circZBTB46 pull-down compared to control, highlighting specific microRNAs enriched in the circZBTB46 fraction. (G) Relative expression levels of microRNAs (miR_497-5p, miR_222-5p, miR_22-3p, miR_10a-5p, and miR_25-3p) in ALK(+) ALCL primary samples versus reactive lymph nodes (RLNs), as assessed by small RNA sequencing. (H) Relative expression of miR25-3p in crizotinib-sensitive (Pio) and resistant COSTR200 cells transfected with a negative control mimic (mimicCTL) or mimic_25-3p measured by RT-qPCR. Snord44 was used as an internal control. Data are shown as 2-ΔΔCt relative values . (I) Western blot analysis of PIP5K1C protein levels in PIO and COSTR200 cells transfected with a miR_25-3p mimic or control mimic. GAPDH served as a loading control. Experiments were performed in triplicate. Data are presented as mean ± SEM. Statistical significance was determined using an unpaired two-tailed Student t test with Welch correction: P < 0.05 ( * ), P < 0.001 ( ** ), ns = not significant
    Figure Legend Snippet: circZBTB46 modulates PIP5K1C by sponging miR-25. (A) Volcano plot showing differentially expressed genes in crizotinib-resistant cells established from MTK PDX-derived cells transfected with control siRNA (siCTL) or siRNAs targeting circZBTB46 (siCircZBTB46#1 and #2). (B) Expression of PIP5K1C at the mRNA (top panel, RTLqPCR) and protein (bottom panel, Western blot) levels in COST, MTK-PDX and COSTR200 ALK(+) ALCL cells after circZBTB46 siRNA transfection (48 h). (C) Expression of PIP5K1C at the mRNA (left panel) and protein (right panel) levels in stable COSTR200 cells expressing either control shRNA (CTL) or shRNA targeting circZBTB46, as assessed by RTLqPCR and Western blot, respectively. (D) Expression of PIP5K1C in Pio ALK(+) ALCL cells stably expressing Cas13 with control gRNA (CTL) or gRNA targeting circZBTB46, as determined by RTLqPCR (left panel) and immunoblotting (right panel), respectively. (E) RNA enrichment after RNA pull-down using biotinylated probes targeting circZBTB46 or control probes . (F) Volcano plot showing in the COST cell line differentially enriched RNAs in circZBTB46 pull-down compared to control, highlighting specific microRNAs enriched in the circZBTB46 fraction. (G) Relative expression levels of microRNAs (miR_497-5p, miR_222-5p, miR_22-3p, miR_10a-5p, and miR_25-3p) in ALK(+) ALCL primary samples versus reactive lymph nodes (RLNs), as assessed by small RNA sequencing. (H) Relative expression of miR25-3p in crizotinib-sensitive (Pio) and resistant COSTR200 cells transfected with a negative control mimic (mimicCTL) or mimic_25-3p measured by RT-qPCR. Snord44 was used as an internal control. Data are shown as 2-ΔΔCt relative values . (I) Western blot analysis of PIP5K1C protein levels in PIO and COSTR200 cells transfected with a miR_25-3p mimic or control mimic. GAPDH served as a loading control. Experiments were performed in triplicate. Data are presented as mean ± SEM. Statistical significance was determined using an unpaired two-tailed Student t test with Welch correction: P < 0.05 ( * ), P < 0.001 ( ** ), ns = not significant

    Techniques Used: Derivative Assay, Transfection, Control, Expressing, Western Blot, shRNA, Stable Transfection, RNA Sequencing, Negative Control, Quantitative RT-PCR, Two Tailed Test

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    Article Title: Overexpression of Mcl-1 in Anaplastic Large Cell Lymphoma Cell Lines and Tumors
    Article Snippet: initially analyzed Mcl-1 expression in five ALK+ ALCL cell lines using Western blotting methods and a polyclonal antibody (DAKO, Carpinteria, CA). .. The panel of ALK+ ALCL cell lines included Karpas 299 (a gift from Dr. M. Kadin, Boston, MA), SR-786 and SU-DHL-1 (both from DSMZ, Braunschweig, Germany), and JB-6 and TS-G1 (gifts from Dr. D. Jones, Houston, TX). .. All five cell lines have been shown to carry t(2;5) and overexpress ALK.

    Western Blot:

    Article Title: Overexpression of Mcl-1 in Anaplastic Large Cell Lymphoma Cell Lines and Tumors
    Article Snippet: initially analyzed Mcl-1 expression in five ALK+ ALCL cell lines using Western blotting methods and a polyclonal antibody (DAKO, Carpinteria, CA). .. The panel of ALK+ ALCL cell lines included Karpas 299 (a gift from Dr. M. Kadin, Boston, MA), SR-786 and SU-DHL-1 (both from DSMZ, Braunschweig, Germany), and JB-6 and TS-G1 (gifts from Dr. D. Jones, Houston, TX). .. All five cell lines have been shown to carry t(2;5) and overexpress ALK.



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    DSMZ anaplastic large cell lymphoma alcl cell lines
    a, The scheme shows the workflow of the study. Enriched circRNA fractions of 4 pairs of sensitive and resistant ALK+ <t>ALCL</t> cell models (Karpas-299, SUP-M2, SU-DHL-1, COST) were sequenced in full-length using ONT. Identified resistance-associated isoforms were validated in vitro and in vivo . b, circRNA isoforms were bioinformatically detected with the tools CIRI-long and circFL-seq in the ALKi sensitive (n=4 biologically independent samples) and resistant (n=4 biologically independent samples) groups. The overlap of detected circRNAs is shown as a Venn diagram. circRNAs commonly detected are used as a robust dataset for downstr 2 e 1 am analysis. c, Mean length (nt) of circRNA isoforms by cell line and in the ALKi sensitive (blue) and resistant (red) groups. Data are presented as boxplots. d, Total number of distinct circRNA isoforms in the ALKi sensitive (blue) and resistant (red) groups. The overlap of circRNAs isoforms between the 2 groups is shown as a Venn diagram. e, Density of total distinct circRNA isoforms per chromosome was calculated and normalized to the total coding gene length for each chromosome. The normalized density for both sensitive (blue) and resistant (red) cell models per chromosome is reported. f, Hotspot genes that produce more than 15 distinct circRNA isoforms are shown in the 2 groups from e. In boxplots the center line represents the median, boxes indicate the interquartile range, the whiskers show the 1.5 interquartile range. Data are represented as a barplot showing the absolute number. Source data are provided as a source data file.
    Anaplastic Large Cell Lymphoma Alcl Cell Lines, supplied by DSMZ, used in various techniques. Bioz Stars score: 94/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Fig. 4 Decreased TET2 expression led to a reduction in TXNIP levels by downregulating 5hmC levels. A 5hmC coverage depth (per base pair per peak per 10 million mapped reads) of 5hmC peaks (− 2 kb to + 2 kb) in TET2-knockdown ALCL cell lines and controls. B The Venn diagram of genes associated with downregulated enrichment peaks in RNA-seq from TET2 knockdown ALCL cell lines, 5hmC downregulated genes identified through hMeDIP-seq in TET2 knockdown ALCL cell lines, and cell cycle-related gene sets (GO: 0051301, GO: 0007049). C The TXNIP mRNA expression in TET2 knockdown ALCL cell lines and controls was determined by qPCR (n = 3). D The TXNIP protein expression in TET2 knockdown ALCL cell lines and controls was determined by Western blot (n = 3). E Representative 5hmC sites in TXNIP genes represented by integrative genomics viewer. F 5hmC enrichment in TXNIP of TET2 knockdown ALCL cell lines and controls measured by hMeDIP-qPCR (n = 3). G The Analysis of TET2 recruitment at the TXNIP gene in TET2 knockdown ALCL cell lines and controls was determined by CHIP-qPCR (n = 3). H Representative IHC staining of TXNIP with in ALCL samples (n = 46) and reactive lymph nodes (n = 24). I IHC score analysis for TXNIP in ALCL samples (n = 46) and reactive lymph nodes (n = 24). J Correlation of TXNIP expression and TET2 expression in ALCL samples (n = 46). hMeDIP, Hydroxymethylated DNA Immunoprecipitation; CHIP, Chromatin Immunoprecipitation. Data were expressed as the mean ± SDs. *p < 0.05; **p < 0.01; ***p < 0.001

    Journal: Clinical epigenetics

    Article Title: TET2-mediated 5-hydroxymethylcytosine of TXNIP promotes cell cycle arrest in systemic anaplastic large cell lymphoma.

    doi: 10.1186/s13148-025-01816-0

    Figure Lengend Snippet: Fig. 4 Decreased TET2 expression led to a reduction in TXNIP levels by downregulating 5hmC levels. A 5hmC coverage depth (per base pair per peak per 10 million mapped reads) of 5hmC peaks (− 2 kb to + 2 kb) in TET2-knockdown ALCL cell lines and controls. B The Venn diagram of genes associated with downregulated enrichment peaks in RNA-seq from TET2 knockdown ALCL cell lines, 5hmC downregulated genes identified through hMeDIP-seq in TET2 knockdown ALCL cell lines, and cell cycle-related gene sets (GO: 0051301, GO: 0007049). C The TXNIP mRNA expression in TET2 knockdown ALCL cell lines and controls was determined by qPCR (n = 3). D The TXNIP protein expression in TET2 knockdown ALCL cell lines and controls was determined by Western blot (n = 3). E Representative 5hmC sites in TXNIP genes represented by integrative genomics viewer. F 5hmC enrichment in TXNIP of TET2 knockdown ALCL cell lines and controls measured by hMeDIP-qPCR (n = 3). G The Analysis of TET2 recruitment at the TXNIP gene in TET2 knockdown ALCL cell lines and controls was determined by CHIP-qPCR (n = 3). H Representative IHC staining of TXNIP with in ALCL samples (n = 46) and reactive lymph nodes (n = 24). I IHC score analysis for TXNIP in ALCL samples (n = 46) and reactive lymph nodes (n = 24). J Correlation of TXNIP expression and TET2 expression in ALCL samples (n = 46). hMeDIP, Hydroxymethylated DNA Immunoprecipitation; CHIP, Chromatin Immunoprecipitation. Data were expressed as the mean ± SDs. *p < 0.05; **p < 0.01; ***p < 0.001

    Article Snippet: The ALK + ALCL cell line Su-DHL-1 was purchased from the American Type Culture Collection (ATCC).

    Techniques: Expressing, Knockdown, RNA Sequencing, Western Blot, ChIP-qPCR, Immunohistochemistry, Immunoprecipitation, Chromatin Immunoprecipitation

    Fig. 6 Schematic diagram. The schematic of TET2-mediated 5hmC modification of TXNIP promotes the ALCL cell cycle progression and proliferation, as created by Figdraw

    Journal: Clinical epigenetics

    Article Title: TET2-mediated 5-hydroxymethylcytosine of TXNIP promotes cell cycle arrest in systemic anaplastic large cell lymphoma.

    doi: 10.1186/s13148-025-01816-0

    Figure Lengend Snippet: Fig. 6 Schematic diagram. The schematic of TET2-mediated 5hmC modification of TXNIP promotes the ALCL cell cycle progression and proliferation, as created by Figdraw

    Article Snippet: The ALK + ALCL cell line Su-DHL-1 was purchased from the American Type Culture Collection (ATCC).

    Techniques: Modification

    (A) Volcano plot and (B) MA plot of circular RNA expression comparing ALK(+) ALCL primary biopsies (n=39) and healthy tissues (reactive lymph nodes, RLN, n=9). (C) expression of circZBTB46 (left) and ZBTB46 mRNA (right) assessed by RNA-Seq in ALK(+) ALCL primary samples versus RLN. (D) ZBTB46 mRNA expression (RMA) from microarray datasets in ALK(+) ALCL (n=61), angioimmunoblastic T-cell lymphoma (AITL, n=83) and peripheral T-cell lymphoma not otherwise specified (PTCL-NOS, n=71) primary biopsies. (E) ZBTB46 mRNA expression (log2 of the transcript count per million (lenghScaled TPM) from RNA-Seq data in five ALK(+) ALCL cell lines (KARPAS-299, SU-DHL-1, SUP-M2, Pio, COST), two ALK(-) ALCL cell lines (FEPD, MAC-2A) and CD3(+) lymphocytes stimulated (S, n=3) or not (NS, n=3). (F) Quantitative real-time PCR (RTLqPCR) analysis of circZBTB46 and ZBTB46 mRNAs in the same cell types. MLN51 was used as an internal control. Values are expressed as 2^(–Δ)Ct relative ratios. Experiments were performed at least in triplicate. Statistical significance was assessed via an unpaired two-tailed Student’s t test with Welch’s correction: P < 0.01 ( ** ), P < 0.001 (*** ), P < 0.0001 (**** ), ns = not significant. Data are expressed as means ± SD. (G) ZBTB46 mRNA expression across hematological malignancies in the Cancer Cell Line Encyclopedia (CCLE) dataset. (H) Representative immunohistochemical image of an ALK(+) ALCL primary tumor showing ZBTB46 (brown, arrowhead) and CD68 (red, arrow) expression. Cell nuclei were counterstained with hematoxylin (blue). Original magnification, ×24.6.

    Journal: bioRxiv

    Article Title: CircZBTB46, a promising therapeutic target in crizotinib resistant ALK-positive T lymphomas

    doi: 10.64898/2026.01.13.699235

    Figure Lengend Snippet: (A) Volcano plot and (B) MA plot of circular RNA expression comparing ALK(+) ALCL primary biopsies (n=39) and healthy tissues (reactive lymph nodes, RLN, n=9). (C) expression of circZBTB46 (left) and ZBTB46 mRNA (right) assessed by RNA-Seq in ALK(+) ALCL primary samples versus RLN. (D) ZBTB46 mRNA expression (RMA) from microarray datasets in ALK(+) ALCL (n=61), angioimmunoblastic T-cell lymphoma (AITL, n=83) and peripheral T-cell lymphoma not otherwise specified (PTCL-NOS, n=71) primary biopsies. (E) ZBTB46 mRNA expression (log2 of the transcript count per million (lenghScaled TPM) from RNA-Seq data in five ALK(+) ALCL cell lines (KARPAS-299, SU-DHL-1, SUP-M2, Pio, COST), two ALK(-) ALCL cell lines (FEPD, MAC-2A) and CD3(+) lymphocytes stimulated (S, n=3) or not (NS, n=3). (F) Quantitative real-time PCR (RTLqPCR) analysis of circZBTB46 and ZBTB46 mRNAs in the same cell types. MLN51 was used as an internal control. Values are expressed as 2^(–Δ)Ct relative ratios. Experiments were performed at least in triplicate. Statistical significance was assessed via an unpaired two-tailed Student’s t test with Welch’s correction: P < 0.01 ( ** ), P < 0.001 (*** ), P < 0.0001 (**** ), ns = not significant. Data are expressed as means ± SD. (G) ZBTB46 mRNA expression across hematological malignancies in the Cancer Cell Line Encyclopedia (CCLE) dataset. (H) Representative immunohistochemical image of an ALK(+) ALCL primary tumor showing ZBTB46 (brown, arrowhead) and CD68 (red, arrow) expression. Cell nuclei were counterstained with hematoxylin (blue). Original magnification, ×24.6.

    Article Snippet: The ALCL cell lines KARPAS-299, SU-DHL-1 SUPM2, Pio and COST, which carry the t(2;5)(p23;q35) translocation, were obtained from the DSMZ (German Collection of Microorganisms and Cell Culture, Leibnitz, Germany) or established locally .

    Techniques: RNA Expression, Expressing, RNA Sequencing, Microarray, Real-time Polymerase Chain Reaction, Control, Two Tailed Test, Immunohistochemical staining

    (A) Relative expression of circZBTB46 and ZBTB46 mRNAs in COST and KARPAS-299 cells transfected for 48 h with control siRNA (siCTL) or two different circZBTB46-targeting siRNAs (siCircZBTB46#1 and #2), as measured by RTLqPCR. (B) Viability (Annexin V-Pacific Blue/PI flow cytometry) of COST and KARPAS-299 cells transfected with siCircZBTB46#1 or #2 and subsequently treated with crizotinib (3 µM, 48 h). (C) Relative expression of circZBTB46 and ZBTB46 mRNAs in COST, SUPM2 and Pio cells transduced with Cas13 and either control gRNA (CTL) or gRNA targeting circZBTB46, as assessed by RTLqPCR. (D) Viability (Annexin V-Pacific Blue/PI flow cytometry) of COST, SUPM2 and Pio cells transduced as described in (C) and treated with crizotinib (100 or 200 nM) for 7 days. ( E ) Relative expression of circZBTB46 and ZBTB46 mRNAs in crizotinib-resistant cells established from MTK PDX-derived cells transfected for 48 h with control siRNA (siCTL) or two different siRNAs targeting circZBTB46 (siCircZBTB46#1 and #2), as measured by RTLqPCR. ( F-G ) Cell viability assessed by Annexin V-Pacific Blue/PI staining (flow cytometry) in crizotinib-resistant cells established from MTK PDX-derived cells transfected with siCircZBTB46#1 or #2, without treatment ( F ) or after crizotinib exposure ( G ) (400 nM, 48 h). ( H ) Relative expression of circZBTB46 and ZBTB46 mRNAs in COST crizotinib-resistant cells (COSTR200) after lentiviral transduction with circZBTB46-targeting shRNAs, as measured by RTLqPCR. ( I ) Viability of COSTR200 cells determined by Annexin V/PI staining (flow cytometry) after transduction with circZBTB46 shRNA and subsequent treatment with crizotinib (1,000 nM, 7 days). MLN51 was used as an internal control for RTLqPCR. Expression data are displayed as 2-ΔΔCt relative values. Statistical significance was assessed via an unpaired two-tailed Student t test with Welch correction: P < 0.05 ( * ), P < 0.01 (** ), P < 0.0001 ( **** ), ns = not significant. Data are expressed as means ± SEMs.

    Journal: bioRxiv

    Article Title: CircZBTB46, a promising therapeutic target in crizotinib resistant ALK-positive T lymphomas

    doi: 10.64898/2026.01.13.699235

    Figure Lengend Snippet: (A) Relative expression of circZBTB46 and ZBTB46 mRNAs in COST and KARPAS-299 cells transfected for 48 h with control siRNA (siCTL) or two different circZBTB46-targeting siRNAs (siCircZBTB46#1 and #2), as measured by RTLqPCR. (B) Viability (Annexin V-Pacific Blue/PI flow cytometry) of COST and KARPAS-299 cells transfected with siCircZBTB46#1 or #2 and subsequently treated with crizotinib (3 µM, 48 h). (C) Relative expression of circZBTB46 and ZBTB46 mRNAs in COST, SUPM2 and Pio cells transduced with Cas13 and either control gRNA (CTL) or gRNA targeting circZBTB46, as assessed by RTLqPCR. (D) Viability (Annexin V-Pacific Blue/PI flow cytometry) of COST, SUPM2 and Pio cells transduced as described in (C) and treated with crizotinib (100 or 200 nM) for 7 days. ( E ) Relative expression of circZBTB46 and ZBTB46 mRNAs in crizotinib-resistant cells established from MTK PDX-derived cells transfected for 48 h with control siRNA (siCTL) or two different siRNAs targeting circZBTB46 (siCircZBTB46#1 and #2), as measured by RTLqPCR. ( F-G ) Cell viability assessed by Annexin V-Pacific Blue/PI staining (flow cytometry) in crizotinib-resistant cells established from MTK PDX-derived cells transfected with siCircZBTB46#1 or #2, without treatment ( F ) or after crizotinib exposure ( G ) (400 nM, 48 h). ( H ) Relative expression of circZBTB46 and ZBTB46 mRNAs in COST crizotinib-resistant cells (COSTR200) after lentiviral transduction with circZBTB46-targeting shRNAs, as measured by RTLqPCR. ( I ) Viability of COSTR200 cells determined by Annexin V/PI staining (flow cytometry) after transduction with circZBTB46 shRNA and subsequent treatment with crizotinib (1,000 nM, 7 days). MLN51 was used as an internal control for RTLqPCR. Expression data are displayed as 2-ΔΔCt relative values. Statistical significance was assessed via an unpaired two-tailed Student t test with Welch correction: P < 0.05 ( * ), P < 0.01 (** ), P < 0.0001 ( **** ), ns = not significant. Data are expressed as means ± SEMs.

    Article Snippet: The ALCL cell lines KARPAS-299, SU-DHL-1 SUPM2, Pio and COST, which carry the t(2;5)(p23;q35) translocation, were obtained from the DSMZ (German Collection of Microorganisms and Cell Culture, Leibnitz, Germany) or established locally .

    Techniques: Expressing, Transfection, Control, Flow Cytometry, Transduction, Derivative Assay, Staining, shRNA, Two Tailed Test

    circZBTB46 modulates PIP5K1C by sponging miR-25. (A) Volcano plot showing differentially expressed genes in crizotinib-resistant cells established from MTK PDX-derived cells transfected with control siRNA (siCTL) or siRNAs targeting circZBTB46 (siCircZBTB46#1 and #2). (B) Expression of PIP5K1C at the mRNA (top panel, RTLqPCR) and protein (bottom panel, Western blot) levels in COST, MTK-PDX and COSTR200 ALK(+) ALCL cells after circZBTB46 siRNA transfection (48 h). (C) Expression of PIP5K1C at the mRNA (left panel) and protein (right panel) levels in stable COSTR200 cells expressing either control shRNA (CTL) or shRNA targeting circZBTB46, as assessed by RTLqPCR and Western blot, respectively. (D) Expression of PIP5K1C in Pio ALK(+) ALCL cells stably expressing Cas13 with control gRNA (CTL) or gRNA targeting circZBTB46, as determined by RTLqPCR (left panel) and immunoblotting (right panel), respectively. (E) RNA enrichment after RNA pull-down using biotinylated probes targeting circZBTB46 or control probes . (F) Volcano plot showing in the COST cell line differentially enriched RNAs in circZBTB46 pull-down compared to control, highlighting specific microRNAs enriched in the circZBTB46 fraction. (G) Relative expression levels of microRNAs (miR_497-5p, miR_222-5p, miR_22-3p, miR_10a-5p, and miR_25-3p) in ALK(+) ALCL primary samples versus reactive lymph nodes (RLNs), as assessed by small RNA sequencing. (H) Relative expression of miR25-3p in crizotinib-sensitive (Pio) and resistant COSTR200 cells transfected with a negative control mimic (mimicCTL) or mimic_25-3p measured by RT-qPCR. Snord44 was used as an internal control. Data are shown as 2-ΔΔCt relative values . (I) Western blot analysis of PIP5K1C protein levels in PIO and COSTR200 cells transfected with a miR_25-3p mimic or control mimic. GAPDH served as a loading control. Experiments were performed in triplicate. Data are presented as mean ± SEM. Statistical significance was determined using an unpaired two-tailed Student t test with Welch correction: P < 0.05 ( * ), P < 0.001 ( ** ), ns = not significant

    Journal: bioRxiv

    Article Title: CircZBTB46, a promising therapeutic target in crizotinib resistant ALK-positive T lymphomas

    doi: 10.64898/2026.01.13.699235

    Figure Lengend Snippet: circZBTB46 modulates PIP5K1C by sponging miR-25. (A) Volcano plot showing differentially expressed genes in crizotinib-resistant cells established from MTK PDX-derived cells transfected with control siRNA (siCTL) or siRNAs targeting circZBTB46 (siCircZBTB46#1 and #2). (B) Expression of PIP5K1C at the mRNA (top panel, RTLqPCR) and protein (bottom panel, Western blot) levels in COST, MTK-PDX and COSTR200 ALK(+) ALCL cells after circZBTB46 siRNA transfection (48 h). (C) Expression of PIP5K1C at the mRNA (left panel) and protein (right panel) levels in stable COSTR200 cells expressing either control shRNA (CTL) or shRNA targeting circZBTB46, as assessed by RTLqPCR and Western blot, respectively. (D) Expression of PIP5K1C in Pio ALK(+) ALCL cells stably expressing Cas13 with control gRNA (CTL) or gRNA targeting circZBTB46, as determined by RTLqPCR (left panel) and immunoblotting (right panel), respectively. (E) RNA enrichment after RNA pull-down using biotinylated probes targeting circZBTB46 or control probes . (F) Volcano plot showing in the COST cell line differentially enriched RNAs in circZBTB46 pull-down compared to control, highlighting specific microRNAs enriched in the circZBTB46 fraction. (G) Relative expression levels of microRNAs (miR_497-5p, miR_222-5p, miR_22-3p, miR_10a-5p, and miR_25-3p) in ALK(+) ALCL primary samples versus reactive lymph nodes (RLNs), as assessed by small RNA sequencing. (H) Relative expression of miR25-3p in crizotinib-sensitive (Pio) and resistant COSTR200 cells transfected with a negative control mimic (mimicCTL) or mimic_25-3p measured by RT-qPCR. Snord44 was used as an internal control. Data are shown as 2-ΔΔCt relative values . (I) Western blot analysis of PIP5K1C protein levels in PIO and COSTR200 cells transfected with a miR_25-3p mimic or control mimic. GAPDH served as a loading control. Experiments were performed in triplicate. Data are presented as mean ± SEM. Statistical significance was determined using an unpaired two-tailed Student t test with Welch correction: P < 0.05 ( * ), P < 0.001 ( ** ), ns = not significant

    Article Snippet: The ALCL cell lines KARPAS-299, SU-DHL-1 SUPM2, Pio and COST, which carry the t(2;5)(p23;q35) translocation, were obtained from the DSMZ (German Collection of Microorganisms and Cell Culture, Leibnitz, Germany) or established locally .

    Techniques: Derivative Assay, Transfection, Control, Expressing, Western Blot, shRNA, Stable Transfection, RNA Sequencing, Negative Control, Quantitative RT-PCR, Two Tailed Test

    Age at diagnosis according to IL10 and TLR3 SNPs. Boxplots displaying median and interquartile ranges of ALK-positive ALCL patients age at diagnosis according to the genotype of selected SNPs. rs1800872 is shown in ( A ), rs1800896 in ( B ) and rs3775291 in ( C ). Dominant or recessive behavior of the variant allele was tested by grouping patients bearing at least one variant or reference allele (middle and right panels). Mann-Whitney test was used to calculate statistical significance, expressed as p values and *. * p < 0.05, ** p < 0.01

    Journal: Journal of Translational Medicine

    Article Title: Association of immune relevant single nucleotide polymorphisms with ALK-positive anaplastic large cell lymphoma presentation and outcome: results of the immuno ALCL study

    doi: 10.1186/s12967-025-07410-5

    Figure Lengend Snippet: Age at diagnosis according to IL10 and TLR3 SNPs. Boxplots displaying median and interquartile ranges of ALK-positive ALCL patients age at diagnosis according to the genotype of selected SNPs. rs1800872 is shown in ( A ), rs1800896 in ( B ) and rs3775291 in ( C ). Dominant or recessive behavior of the variant allele was tested by grouping patients bearing at least one variant or reference allele (middle and right panels). Mann-Whitney test was used to calculate statistical significance, expressed as p values and *. * p < 0.05, ** p < 0.01

    Article Snippet: Human NPM1::ALK-positive anaplastic large cell lymphoma (ALCL) SU-DHL-1 cell line was purchased from the German Collection of Microorganisms and Cell Cultures (DSMZ, Braunschweig, Germany) and cultured in RPMI 1640 supplemented with 100 units/mL of penicillin, 100 μg/mL of streptomycin (Pen/Strep) and 10% fetal bovine serum (FBS).

    Techniques: Biomarker Discovery, Variant Assay, MANN-WHITNEY

    Progression-free survival of ALK-positive ALCL-patients according to selected SNP genotypes. Kaplan-Meier plots displaying progression-free survival of patients with ALK-positive ALCL after chemotherapy. Patients were categorized according to selected SNP genotypes. IFNGR2 rs17882748 is shown in ( A ), TLR3 rs3775291 in ( B ) and CD86 rs1129055 in ( C ). Dominant or recessive behavior of the variant allele was tested by grouping patients bearing at least one variant or reference allele (middle and right panels). Observations of patients alive without failure were censored at the time of their last follow-up and indicated by a cross on the curve at the censoring time. Log-rank test was used to calculate statistical significance, expressed as p values and *. * p < 0.05. Numbers at the bottom of the figure are number at risk

    Journal: Journal of Translational Medicine

    Article Title: Association of immune relevant single nucleotide polymorphisms with ALK-positive anaplastic large cell lymphoma presentation and outcome: results of the immuno ALCL study

    doi: 10.1186/s12967-025-07410-5

    Figure Lengend Snippet: Progression-free survival of ALK-positive ALCL-patients according to selected SNP genotypes. Kaplan-Meier plots displaying progression-free survival of patients with ALK-positive ALCL after chemotherapy. Patients were categorized according to selected SNP genotypes. IFNGR2 rs17882748 is shown in ( A ), TLR3 rs3775291 in ( B ) and CD86 rs1129055 in ( C ). Dominant or recessive behavior of the variant allele was tested by grouping patients bearing at least one variant or reference allele (middle and right panels). Observations of patients alive without failure were censored at the time of their last follow-up and indicated by a cross on the curve at the censoring time. Log-rank test was used to calculate statistical significance, expressed as p values and *. * p < 0.05. Numbers at the bottom of the figure are number at risk

    Article Snippet: Human NPM1::ALK-positive anaplastic large cell lymphoma (ALCL) SU-DHL-1 cell line was purchased from the German Collection of Microorganisms and Cell Cultures (DSMZ, Braunschweig, Germany) and cultured in RPMI 1640 supplemented with 100 units/mL of penicillin, 100 μg/mL of streptomycin (Pen/Strep) and 10% fetal bovine serum (FBS).

    Techniques: Variant Assay

    Progression-free survival of ALK-positive ALCL-patients according to selected combination of SNPs. Kaplan-Meier plots displaying progression-free survival of patients with ALK-positive ALCL after chemotherapy. Patients were categorized according to selected combination of SNPs after scoring, rs1129055 and rs231775 ( A ), rs1800896 and rs1129055 ( B ), rs1129055 and rs867228 ( C ), rs3751143 and rs3775291 ( D ), rs3751143 and rs4143815 ( E ), rs17882748 and rs3775291 ( F ), rs1041868 and rs3775291 ( G ), rs17882748 and rs231775 ( H ), rs17882748 and rs1129055 ( I ), rs867228 and rs231775 ( J ). Observations of patients alive without failure were censored at the time of their last follow-up and indicated by a cross on the curve at the censoring time. Log-rank test was used to calculate statistical significance, expressed as p values and *. * p < 0.05.

    Journal: Journal of Translational Medicine

    Article Title: Association of immune relevant single nucleotide polymorphisms with ALK-positive anaplastic large cell lymphoma presentation and outcome: results of the immuno ALCL study

    doi: 10.1186/s12967-025-07410-5

    Figure Lengend Snippet: Progression-free survival of ALK-positive ALCL-patients according to selected combination of SNPs. Kaplan-Meier plots displaying progression-free survival of patients with ALK-positive ALCL after chemotherapy. Patients were categorized according to selected combination of SNPs after scoring, rs1129055 and rs231775 ( A ), rs1800896 and rs1129055 ( B ), rs1129055 and rs867228 ( C ), rs3751143 and rs3775291 ( D ), rs3751143 and rs4143815 ( E ), rs17882748 and rs3775291 ( F ), rs1041868 and rs3775291 ( G ), rs17882748 and rs231775 ( H ), rs17882748 and rs1129055 ( I ), rs867228 and rs231775 ( J ). Observations of patients alive without failure were censored at the time of their last follow-up and indicated by a cross on the curve at the censoring time. Log-rank test was used to calculate statistical significance, expressed as p values and *. * p < 0.05.

    Article Snippet: Human NPM1::ALK-positive anaplastic large cell lymphoma (ALCL) SU-DHL-1 cell line was purchased from the German Collection of Microorganisms and Cell Cultures (DSMZ, Braunschweig, Germany) and cultured in RPMI 1640 supplemented with 100 units/mL of penicillin, 100 μg/mL of streptomycin (Pen/Strep) and 10% fetal bovine serum (FBS).

    Techniques:

    IL10 and TLR3 expression levels according to rs1800872, rs1800896 and rs3775291 genotypes. IL10 and TLR3 mRNA levels in circulating PBMCs of ALK-positive ALCL patients ( n = 85) were assessed using qRT-PCR. Relative expression, as 2^(−ΔCt), is presented according to rs1800872 ( A ), rs1800896 ( B ) or rs3775291 ( C ) genotypes. Statistical significance was calculated using the Student’s t-test with Welch’s correction and expressed as p values and *. * p < 0.05, ** p < 0.01

    Journal: Journal of Translational Medicine

    Article Title: Association of immune relevant single nucleotide polymorphisms with ALK-positive anaplastic large cell lymphoma presentation and outcome: results of the immuno ALCL study

    doi: 10.1186/s12967-025-07410-5

    Figure Lengend Snippet: IL10 and TLR3 expression levels according to rs1800872, rs1800896 and rs3775291 genotypes. IL10 and TLR3 mRNA levels in circulating PBMCs of ALK-positive ALCL patients ( n = 85) were assessed using qRT-PCR. Relative expression, as 2^(−ΔCt), is presented according to rs1800872 ( A ), rs1800896 ( B ) or rs3775291 ( C ) genotypes. Statistical significance was calculated using the Student’s t-test with Welch’s correction and expressed as p values and *. * p < 0.05, ** p < 0.01

    Article Snippet: Human NPM1::ALK-positive anaplastic large cell lymphoma (ALCL) SU-DHL-1 cell line was purchased from the German Collection of Microorganisms and Cell Cultures (DSMZ, Braunschweig, Germany) and cultured in RPMI 1640 supplemented with 100 units/mL of penicillin, 100 μg/mL of streptomycin (Pen/Strep) and 10% fetal bovine serum (FBS).

    Techniques: Expressing, Quantitative RT-PCR

    IL10 mRNA levels, expressed as 2^(−ΔCt), of ALK-positive ALCL patients ( n = 82) are shown against patients age at diagnosis, expressed in months ( A ). Correlation between IL10 expression level and age at diagnosis according to SNP genotype of rs1800872 ( B ) and rs1800896 ( C ). Pearson’s correlation coefficients and statistical significance are shown in the box below the respective graph

    Journal: Journal of Translational Medicine

    Article Title: Association of immune relevant single nucleotide polymorphisms with ALK-positive anaplastic large cell lymphoma presentation and outcome: results of the immuno ALCL study

    doi: 10.1186/s12967-025-07410-5

    Figure Lengend Snippet: IL10 mRNA levels, expressed as 2^(−ΔCt), of ALK-positive ALCL patients ( n = 82) are shown against patients age at diagnosis, expressed in months ( A ). Correlation between IL10 expression level and age at diagnosis according to SNP genotype of rs1800872 ( B ) and rs1800896 ( C ). Pearson’s correlation coefficients and statistical significance are shown in the box below the respective graph

    Article Snippet: Human NPM1::ALK-positive anaplastic large cell lymphoma (ALCL) SU-DHL-1 cell line was purchased from the German Collection of Microorganisms and Cell Cultures (DSMZ, Braunschweig, Germany) and cultured in RPMI 1640 supplemented with 100 units/mL of penicillin, 100 μg/mL of streptomycin (Pen/Strep) and 10% fetal bovine serum (FBS).

    Techniques: Biomarker Discovery, Expressing

    Transcriptome and secretome of ALK-positive ALCL cell line SU-DHL-1. Transcriptomic profile of selected mRNAs of human NPM1::ALK-positive SU-DHL-1 cells treated with the ALK inhibitor ceritinib (50nM) for 24 h. The expression level of immune-relevant transcripts of ceritinib-treated cells were compared to vehicle-treated cells and fold changes (in logarithmic scale) are depicted ( A ). Secretion profile of selected cytokines and immune-checkpoint ligands of human NPM1::ALK-positive SU-DHL-1 cells treated with the ALK inhibitor ceritinib (50nM) for 24–48 h. Cytokine and immune checkpoint ligands levels of ceritinib-treated cells were compared to vehicle-treated cells and fold changes (in logarithmic scale) are depicted ( B ). Statistical significance was calculated using the multiple Student’s t-test. * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001

    Journal: Journal of Translational Medicine

    Article Title: Association of immune relevant single nucleotide polymorphisms with ALK-positive anaplastic large cell lymphoma presentation and outcome: results of the immuno ALCL study

    doi: 10.1186/s12967-025-07410-5

    Figure Lengend Snippet: Transcriptome and secretome of ALK-positive ALCL cell line SU-DHL-1. Transcriptomic profile of selected mRNAs of human NPM1::ALK-positive SU-DHL-1 cells treated with the ALK inhibitor ceritinib (50nM) for 24 h. The expression level of immune-relevant transcripts of ceritinib-treated cells were compared to vehicle-treated cells and fold changes (in logarithmic scale) are depicted ( A ). Secretion profile of selected cytokines and immune-checkpoint ligands of human NPM1::ALK-positive SU-DHL-1 cells treated with the ALK inhibitor ceritinib (50nM) for 24–48 h. Cytokine and immune checkpoint ligands levels of ceritinib-treated cells were compared to vehicle-treated cells and fold changes (in logarithmic scale) are depicted ( B ). Statistical significance was calculated using the multiple Student’s t-test. * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001

    Article Snippet: Human NPM1::ALK-positive anaplastic large cell lymphoma (ALCL) SU-DHL-1 cell line was purchased from the German Collection of Microorganisms and Cell Cultures (DSMZ, Braunschweig, Germany) and cultured in RPMI 1640 supplemented with 100 units/mL of penicillin, 100 μg/mL of streptomycin (Pen/Strep) and 10% fetal bovine serum (FBS).

    Techniques: Expressing

    a, The scheme shows the workflow of the study. Enriched circRNA fractions of 4 pairs of sensitive and resistant ALK+ ALCL cell models (Karpas-299, SUP-M2, SU-DHL-1, COST) were sequenced in full-length using ONT. Identified resistance-associated isoforms were validated in vitro and in vivo . b, circRNA isoforms were bioinformatically detected with the tools CIRI-long and circFL-seq in the ALKi sensitive (n=4 biologically independent samples) and resistant (n=4 biologically independent samples) groups. The overlap of detected circRNAs is shown as a Venn diagram. circRNAs commonly detected are used as a robust dataset for downstr 2 e 1 am analysis. c, Mean length (nt) of circRNA isoforms by cell line and in the ALKi sensitive (blue) and resistant (red) groups. Data are presented as boxplots. d, Total number of distinct circRNA isoforms in the ALKi sensitive (blue) and resistant (red) groups. The overlap of circRNAs isoforms between the 2 groups is shown as a Venn diagram. e, Density of total distinct circRNA isoforms per chromosome was calculated and normalized to the total coding gene length for each chromosome. The normalized density for both sensitive (blue) and resistant (red) cell models per chromosome is reported. f, Hotspot genes that produce more than 15 distinct circRNA isoforms are shown in the 2 groups from e. In boxplots the center line represents the median, boxes indicate the interquartile range, the whiskers show the 1.5 interquartile range. Data are represented as a barplot showing the absolute number. Source data are provided as a source data file.

    Journal: medRxiv

    Article Title: Identification of full-length circular RNAs linked with therapy resistance of pediatric cancers

    doi: 10.64898/2025.11.28.25340833

    Figure Lengend Snippet: a, The scheme shows the workflow of the study. Enriched circRNA fractions of 4 pairs of sensitive and resistant ALK+ ALCL cell models (Karpas-299, SUP-M2, SU-DHL-1, COST) were sequenced in full-length using ONT. Identified resistance-associated isoforms were validated in vitro and in vivo . b, circRNA isoforms were bioinformatically detected with the tools CIRI-long and circFL-seq in the ALKi sensitive (n=4 biologically independent samples) and resistant (n=4 biologically independent samples) groups. The overlap of detected circRNAs is shown as a Venn diagram. circRNAs commonly detected are used as a robust dataset for downstr 2 e 1 am analysis. c, Mean length (nt) of circRNA isoforms by cell line and in the ALKi sensitive (blue) and resistant (red) groups. Data are presented as boxplots. d, Total number of distinct circRNA isoforms in the ALKi sensitive (blue) and resistant (red) groups. The overlap of circRNAs isoforms between the 2 groups is shown as a Venn diagram. e, Density of total distinct circRNA isoforms per chromosome was calculated and normalized to the total coding gene length for each chromosome. The normalized density for both sensitive (blue) and resistant (red) cell models per chromosome is reported. f, Hotspot genes that produce more than 15 distinct circRNA isoforms are shown in the 2 groups from e. In boxplots the center line represents the median, boxes indicate the interquartile range, the whiskers show the 1.5 interquartile range. Data are represented as a barplot showing the absolute number. Source data are provided as a source data file.

    Article Snippet: The human ALK+ ALCL cell lines SU-DHL-1, Karpas-299 and SUP-M2 were obtained from the German Collection of Microorganisms and Cell Culture GmbH (DSMZ, Braunschweig, Germany).

    Techniques: In Vitro, In Vivo

    a, Serum samples of healthy donors (n=10 biologically independent samples) and from patients with ALK+ ALCL (n=4 patients) at diagnosis and after ALKi treatment showing a bad response were analyzed by qRT-PCR. The expression of circSLTM (3,4,5) and circRUNX1 (6,7) are shown. Data are presented as mean ±SD. b, Primary biopsies of patients with ALK+ ALCL with a small-cell containing (n=16 biologically independent samples) or other histological subtype (n=22 biologically independent samples) were analyzed by RNA-seq. c, The patients of b were divided in a group with both circSLTM (3,4,5) and circRUNX1 (6,7) low (n=8) vs. high (n=13) expression and the probability of event-free survival (EFS) in months is shown as a Kaplan-Meier curve. In boxplots the center line represents the median, boxes indicate the interquartile range, the whiskers show the 1.5 interquartile range. Source data are provided as a source data file.

    Journal: medRxiv

    Article Title: Identification of full-length circular RNAs linked with therapy resistance of pediatric cancers

    doi: 10.64898/2025.11.28.25340833

    Figure Lengend Snippet: a, Serum samples of healthy donors (n=10 biologically independent samples) and from patients with ALK+ ALCL (n=4 patients) at diagnosis and after ALKi treatment showing a bad response were analyzed by qRT-PCR. The expression of circSLTM (3,4,5) and circRUNX1 (6,7) are shown. Data are presented as mean ±SD. b, Primary biopsies of patients with ALK+ ALCL with a small-cell containing (n=16 biologically independent samples) or other histological subtype (n=22 biologically independent samples) were analyzed by RNA-seq. c, The patients of b were divided in a group with both circSLTM (3,4,5) and circRUNX1 (6,7) low (n=8) vs. high (n=13) expression and the probability of event-free survival (EFS) in months is shown as a Kaplan-Meier curve. In boxplots the center line represents the median, boxes indicate the interquartile range, the whiskers show the 1.5 interquartile range. Source data are provided as a source data file.

    Article Snippet: The human ALK+ ALCL cell lines SU-DHL-1, Karpas-299 and SUP-M2 were obtained from the German Collection of Microorganisms and Cell Culture GmbH (DSMZ, Braunschweig, Germany).

    Techniques: Biomarker Discovery, Quantitative RT-PCR, Expressing, RNA Sequencing