human alk alcl cell lines su dhl 1  (DSMZ)

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

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

Journal: Journal of Clinical Investigation

Article Title: ALK-transformed mature T lymphocytes restore early thymus progenitor features

doi: 10.1172/jci134990

Figure Lengend Snippet: Figure 1. NPM-ALK dependence of the transformed CD4+ T cells. (A) Expression by qRT-PCR analysis of NPM-ALK mRNA in the transformed CD4+ T cells (CD4-NPM/ALK+ lane shows the mean from 9 independent cell lines) and 3 positive control NPM-ALK+ ALCL cell lines: KARPAS-299, SU-DHL-1, and COST. CD4+ T cells preactivated with CD3/CD28 antibody-coated beads were used as negative controls (preactivated CD4). MLNS1 was used as an internal control. Relative NPM-ALK expression was expressed as the 2–ΔCt relative to MLN51. Data represent mean ± SEM. *P < 0.05, **P < 0.001, ***P < 0.001; unpaired 2-tailed Student’s t test with Welch’s correction. (B) Suppressive effect of the ALK inhibitor crizotinib (500 nmol/L) on ALK and STAT3 phosphorylation in transformed CD4+ T cells and control NPM-ALK+ KARPAS-299 cells. The GAPDH protein served as an internal control to ensure equal loading. Blots from 1 representative experiment are shown.

Article Snippet: The human NPM-ALK+ ALCL cell line COST was established in the laboratory (40) and KARPAS-299 and SU-DHL-1 NPM-ALK+ ALCL cell lines were obtained from DSMZ (German Collection of Microorganisms and Cell Culture, Braunschweig, Germany).

Techniques: Transformation Assay, Expressing, Quantitative RT-PCR, Positive Control, Control, Phospho-proteomics

Journal: Journal of Clinical Investigation

Article Title: ALK-transformed mature T lymphocytes restore early thymus progenitor features

doi: 10.1172/jci134990

Figure Lengend Snippet: Figure 5. DMRs revealed that NPM-ALK–transformed CD4+ T cells and primary NPM-ALK+ ALCL cells have a close similarity with the ETP. (A) We used publicly available methylation data sets (30) generated from different devel- opmental T cell stages (multipotent ETPs [CD34+/CD1a–; n = 2]; T cell–committed progenitors [CD34+/CD1a+; n = 1]; pre- TCR T cells [n = 2]; TCR-expressing CD4+/CD8+ double-pos- itive T cells [DP-TCR+, n = 2]; and single positive [SP] CD8+ or CD4+ cells [SP-CD4+; n = 2 or SP-CD8+; n = 2]) to identify a cluster of 510 DMRs available to discriminate each different stage of T cell differentiation in the thymus. (B) Hierarchical clustering dendrogram using a cluster of 510 DMRs revealed that NPM-ALK–transformed CD4+ T cells were distant to the healthy CD4+ lymphocyte profile and clustered with primary NPM-ALK+ ALCL biopsies. Heatmaps also showed a similar- ity of NPM-ALK+ cells (NPM-ALK–transformed CD4+ T cells and primary patient–derived NPM-ALK+ ALCL) with CD34+/ CD1a– cells corresponding to the ETP stage.

Article Snippet: The human NPM-ALK+ ALCL cell line COST was established in the laboratory (40) and KARPAS-299 and SU-DHL-1 NPM-ALK+ ALCL cell lines were obtained from DSMZ (German Collection of Microorganisms and Cell Culture, Braunschweig, Germany).

Techniques: Transformation Assay, Methylation, Generated, Expressing, Cell Differentiation, Derivative Assay

Journal: Journal of Clinical Investigation

Article Title: ALK-transformed mature T lymphocytes restore early thymus progenitor features

doi: 10.1172/jci134990

Figure Lengend Snippet: Figure 6. DMRs of NPM-ALK–transformed CD4+ T cells and primary patient–derived NPM-ALK+ ALCL cells and the ETP. Two hundred and forty-three among the 510 DMRs within NPM-ALK–transformed CD4+ T cells (CD4+/NPM-ALK+), primary patient–derived NPM-ALK+ ALCL cells, and CD34+/CD1a– cells corresponding to the ETP stage. Venn diagram reveals that the ETP and both the NPM-ALK+ tumor cell entities (CD4+/NPM-ALK+ lymphoma cells and primary NPM-ALK+ ALCLs) share 38 DMRs with similar expression patterns.

Article Snippet: The human NPM-ALK+ ALCL cell line COST was established in the laboratory (40) and KARPAS-299 and SU-DHL-1 NPM-ALK+ ALCL cell lines were obtained from DSMZ (German Collection of Microorganisms and Cell Culture, Braunschweig, Germany).

Techniques: Transformation Assay, Derivative Assay, Expressing

Journal: Journal of Clinical Investigation

Article Title: ALK-transformed mature T lymphocytes restore early thymus progenitor features

doi: 10.1172/jci134990

Figure Lengend Snippet: Figure 7. Transcriptional pattern links NPM-ALK–transformed CD4+ T cells and primary patient–derived NPM-ALK+ ALCL cells to ETP cells. mRNA expression profiles from several cell populations isolated ex vivo from the neonatal human thymus defining in vivo maturation stages, multipotent ETPs (CD34+/CD1a–/CD7–; n = 3), late thymic precursor (CD34+/CD1a–/CD7+; n = 3), T cell–committed progenitors (CD34+/CD1a–/CD7+; n = 3), CD3–/CD4+ imma- ture single-positive (ISP) (ISP-CD4+, n = 4), CD4+/CD8+ double-positive TCR– cells (DP-TCR–; n = 3), and TCR-expressing CD4+/CD8+ double-positive T cells (DP-TCR+, n = 3) were integrated with our previous findings from the gene expression array data of 55 primary NPM-ALK+ ALCL samples (NPM-ALK+ ALCL) (35) and RNA-Seq data from the NPM-ALK–transformed CD4+ T cells (CD4+/NPM-ALK+; n = 9). NPM-ALK CD4+/NPM-ALK+ cells were distant to the healthy CD4+ lymphocyte but close to NPM-ALK+ ALCL. Moreover, NPM-ALK+ cells (NPM-ALK–transformed CD4+ T cells and primary patient–derived NPM-ALK+ ALCL) showed a similarity with the ETP stage.

Article Snippet: The human NPM-ALK+ ALCL cell line COST was established in the laboratory (40) and KARPAS-299 and SU-DHL-1 NPM-ALK+ ALCL cell lines were obtained from DSMZ (German Collection of Microorganisms and Cell Culture, Braunschweig, Germany).

Techniques: Transformation Assay, Derivative Assay, Expressing, Isolation, Ex Vivo, In Vivo, Gene Expression, RNA Sequencing

Journal: Journal of Clinical Investigation

Article Title: ALK-transformed mature T lymphocytes restore early thymus progenitor features

doi: 10.1172/jci134990

Figure Lengend Snippet: Figure 8. HIF2A, encoded by the EPAS1 gene, is strictly dependent on NPM-ALK activity and activation of the STAT3 key signal transduction pathways in lymphoma cells. (A) Quantitative RT-PCR analysis of ALK and EPAS1 mRNA was performed in primary patient–derived NPM-ALK+ ALCL cells (n = 29). Relative mRNA expression was expressed as the 2–ΔΔCt relative to MLN51, S5, ABL, GAPDH, S14, or RPL0 genes for normalization and compared with pre- activated healthy CD4+ lymphocytes (n = 5). Data represent mean ± SEM. ***P < 0.001; unpaired 2-tailed Student’s t test. (B) Quantitative RT-PCR analysis of EPAS1 mRNA expression in NPM-ALK+ lymphoma cell lines, COST, KARPAS-299 (KARPAS), and SU-DHL1, treated for 72 hours or not (PBS) with crizo- tinib or transfected with either an irrelevant siRNA as the negative control (si-CTL) or a siRNA targeting ALK mRNA (si-ALK) or STAT3 (si-STAT3). Relative EPAS1 mRNA expression was expressed as the 2–ΔCt relative to MLN51. Data represent mean ± SEM from 3 independent experiments. *P < 0.05, ***P < 0.001; unpaired 2-tailed Student’s t test with Welch’s correction. (C) Western blotting analysis of HIF2A expression (top) in NPM-ALK+ COST, KARPAS-299, and SU-DHL1 cells treated with crizotinib (crizo) or not (PBS), transfected by si-CTL, si-ALK, or si-STAT3. The GAPDH protein (bottom) served as an internal control to ensure equal loading. Results from 1 representative experiment are shown.

Article Snippet: The human NPM-ALK+ ALCL cell line COST was established in the laboratory (40) and KARPAS-299 and SU-DHL-1 NPM-ALK+ ALCL cell lines were obtained from DSMZ (German Collection of Microorganisms and Cell Culture, Braunschweig, Germany).

Techniques: Activity Assay, Activation Assay, Transduction, Quantitative RT-PCR, Derivative Assay, Expressing, Transfection, Negative Control, Western Blot, Control

Journal: Nature medicine

Article Title: Wiskott–Aldrich syndrome protein (WASP) is a tumor suppressor in T cell lymphoma

doi: 10.1038/s41591-018-0262-9

Figure Lengend Snippet: (a) Western Blot analysis of ALK+ ALCL cell lines (SU-DHL1, JB6, Karpas-299 and DEL) transduced with doxycycline-inducible lentivirus co-expressing WASP and WIP (W&W) or a control reporter GFP (Ctrl). Black arrows: endogenous WASP and WIP; red arrows: Flag-tagged WASP and WIP. MAC-1 cell line and normal T cells were used as controls. The blot is representative of at least two independent experiments with similar results. Actin was used as a loading control. Uncropped blots are available in Supplementary Figure 11.

Article Snippet: Human ALK+ ALCL cell lines (TS, SU-DHL1, JB6, Karpas-299, DEL, SUP-M2 and L82) and ALK- cell lines (MAC-1, FePD and Jurkat) ALCL cell lines were obtained from DSMZ (German collection of Microorganisms and Cell Cultures).

Techniques: Western Blot, Transduction, Expressing, Control

Journal: Nature medicine

Article Title: Wiskott–Aldrich syndrome protein (WASP) is a tumor suppressor in T cell lymphoma

doi: 10.1038/s41591-018-0262-9

Figure Lengend Snippet: (a) Western Blot performed on human ALK+ ALCL cells lines and ALK- T lymphoma lines or normal T cells blotted with the indicated antibodies. The blot is representative of two independent experiments with similar results. Actin was used as a loading control. Uncropped blots are available in Supplementary Figure 11.

Article Snippet: Human ALK+ ALCL cell lines (TS, SU-DHL1, JB6, Karpas-299, DEL, SUP-M2 and L82) and ALK- cell lines (MAC-1, FePD and Jurkat) ALCL cell lines were obtained from DSMZ (German collection of Microorganisms and Cell Cultures).

Techniques: Western Blot, Control

Journal: Nature medicine

Article Title: Wiskott–Aldrich syndrome protein (WASP) is a tumor suppressor in T cell lymphoma

doi: 10.1038/s41591-018-0262-9

Figure Lengend Snippet: (a) Gene-expression profiling analysis of ALK, WASP, WIP, N-WASP, CDC42 and TNFRS8 (CD30) on different cases of human T cell lymphomas: AITL, n = 40; PTCL-NOS, n = 74; ALK- ALCL, n = 24, ALK+ ALCL, n = 30. The boxes represent the first and third quartiles, and the line represents the median. The whiskers represent the upper and lower limits of the range (ALK+ ALCL vs AITL, ****P = 5.85 X 10−6; ALK+ ALCL vs PTCL-NOS, ****P = 6.08 X 10−12; ALK+ ALCL vs ALK- ALCL, **P = 0.0075; significance was determined by unpaired, two-tailed Student’s t-test). TNFRS8 (CD30) is strongly expressed in ALK- or ALK+ ALCL but not in other T cell lymphoma (TCL) subtypes.

Article Snippet: Human ALK+ ALCL cell lines (TS, SU-DHL1, JB6, Karpas-299, DEL, SUP-M2 and L82) and ALK- cell lines (MAC-1, FePD and Jurkat) ALCL cell lines were obtained from DSMZ (German collection of Microorganisms and Cell Cultures).

Techniques: Gene Expression, Two Tailed Test