sudhl 4  (ATCC)

Journal: bioRxiv

Article Title: OSTM1 is a ubiquitin E3 ligase that suppresses B-cell malignancy by activating the cAMP/PKA/CREB pathway

doi: 10.64898/2026.01.23.701155

Figure Lengend Snippet: (A) Genomic alterations of OSTM1 across human cancers were derived from TCGA. Shown are the top 5 cancer types with the most frequent alterations. (B) Frequency of OSTM1 genomic deletions across BCL subtypes from published datasets, including DLBCL, multiple myeloma (MM), follicular lymphoma (FL), B-CLL, and Burkitt lymphoma (BL). (C) OSTM1 log2 copy number variations (CNVs) and percent loss across BCL subtypes in the TCGA Mature B-cell Malignancies dataset (MD Anderson Cancer Center, MDACC). (D) Spearman correlations between fraction genome altered (FGA; genomic instability) and OSTM1 copy number (left) and the Kaplan–Meier survival of patients with or without OSTM1 deletion in the same dataset in mature B-cell malignancies (dataset from C). (E) Correlations between FGA and OSTM1 deletions (left) or mRNA expression levels (right) in DLBCL patients (TCGA Firehose Legacy). (F) OSTM1 mRNA expression in normal lymphoid tissues vs. BCL subtypes using published datasets. (G) qRT-PCR analysis of OSTM1 expression in cell lines from DLBCL, MCL, MM, and BL compared to PBMCs from healthy donors. (H) Kaplan–Meier survival analyses across multiple BCL datasets, stratified by median OSTM1 expression (upper median: high expression; lower median: low expression).

Article Snippet: Human DLBCL cell lines SU-DHL-4 (CRL-2957), SU-DHL-5 (CRL-2958), and SU-DHL-10 (CRL-2963), Burkitt’s lymphoma cell lines Daudi and Ramos, as well as mantle cell lymphoma cell lines Z-138 and JeKo-1 were obtained from American Type Culture Collection (ATCC, Manassas, VA).

Techniques: Derivative Assay, Expressing, Quantitative RT-PCR

Journal: bioRxiv

Article Title: OSTM1 is a ubiquitin E3 ligase that suppresses B-cell malignancy by activating the cAMP/PKA/CREB pathway

doi: 10.64898/2026.01.23.701155

Figure Lengend Snippet: (A) OSTM1 copy number variations (CNVs) were available in DLBCL patients in TCGA Firehose Legacy. While 25% patients had shallow deletion, 12.5% had deep deletion. (B) OSTM1 deletions correlated with decreased mRNA expression in the same patients. (C) RPMI-8226 cell line stably expressing OSTM1-Flag, PBMC isolated from three healthy donors, and indicated BCL cell lines were probed for ectopically expressed or endogenous OSTM1. (D) ImageJ quantification of the ratio between non-glycosylated (∼37 kDa) and glycosylated (∼60 kDa) OSTM1.

Article Snippet: Human DLBCL cell lines SU-DHL-4 (CRL-2957), SU-DHL-5 (CRL-2958), and SU-DHL-10 (CRL-2963), Burkitt’s lymphoma cell lines Daudi and Ramos, as well as mantle cell lymphoma cell lines Z-138 and JeKo-1 were obtained from American Type Culture Collection (ATCC, Manassas, VA).

Techniques: Expressing, Stable Transfection, Isolation

Journal: bioRxiv

Article Title: OSTM1 is a ubiquitin E3 ligase that suppresses B-cell malignancy by activating the cAMP/PKA/CREB pathway

doi: 10.64898/2026.01.23.701155

Figure Lengend Snippet: (A) Oncoprint visualization of OSTM1 and CDKN2A co-deletions across different BCLs as reported in the indicated studies. (B) Frequencies of CDKN2A deletions among patients with OSTM1 deletions across BCLs (left), and the frequencies of OSTM1 deletion among patients with CDKN2A deletions (right), in the indicated studies. (C) Progression-free survival of DLBCL patients stratified by the presence of chr. 6q deletion ( OSTM1 DEL), 9p21.3 deletion ( CDKN2A DEL), both ( Co-DEL ), or neither (WT). Patients with co-deletions had worse survival. ( D ) Frequencies of individual clonotypes obtained from Igh V(D)J sequencing of mouse spleen samples. Each clonotype is color-coded according to its rank of prevalence within the corresponding sample. ( E ) Comparison of the frequency of the most expanded clonotype across samples, grouped by genotype. ( F ) Percent identity between BCL Igh V(D)J sequences and their corresponding germline sequences, grouped by genotype.

Article Snippet: Human DLBCL cell lines SU-DHL-4 (CRL-2957), SU-DHL-5 (CRL-2958), and SU-DHL-10 (CRL-2963), Burkitt’s lymphoma cell lines Daudi and Ramos, as well as mantle cell lymphoma cell lines Z-138 and JeKo-1 were obtained from American Type Culture Collection (ATCC, Manassas, VA).

Techniques: Sequencing, Comparison

Journal: bioRxiv

Article Title: OSTM1 is a ubiquitin E3 ligase that suppresses B-cell malignancy by activating the cAMP/PKA/CREB pathway

doi: 10.64898/2026.01.23.701155

Figure Lengend Snippet: (A) Left: Pie chart showing the percentage of DLBCL patients with chr. 11p amplification (17.4%). Right: Pie chart showing the fraction of DLBCL patients (n = 48, TCGA Firehose Legacy) with PDE3B amplification (16.7%). (B) Percentage of patients with PDE3B gains across B-cell malignancies (TCGA, MDACC dataset), with individual log2 copy-number values overlaid. (C) Spearman correlation between PDE3B log2 copy-number value and fraction genome altered (FGA) in mature B-cell malignancies. (D) PDE3B expression across indicated BCL cohorts, comparing normal B cells with BCLs; P values were calculated by grouping all normal samples and cancer samples separately and comparing the two groups using Student’s t-test. (E) DLBCL patient samples were obtained from the Rutgers Cancer Institute. The tumor tissue lysates and PBMC from a healthy donor were probed for PDE3B expression. (F) Kaplan-Meier survival curves in DLBCL (GSE4475) and multiple myeloma (GSE2658) patients showing reduced survival in patients with high PDE3B expression, stratified by median expression. (G) PDE3B-His was stably expressed in Ba/F3 cells. Cells were cultured in the presence or absence of IL3, and cell growth was determined by counting cell numbers. ****p<0.0001. (H) PDE3B was detected by IB across cell lines from different BCL subtypes. (I) PDE3B-His was stably expressed in indicated BCL cell lines, and cell proliferation was measured. ***p<0.001. (J and K) PDE3B was silenced with 2 sgRNAs in RPMI-8226 and OPM2 cell lines. Cell proliferation was measured. P-value calculation was done using multiple t-test comparisons, one per row ***p<0.001; ****p<0.0001. (L and M) Spleens from two-month-old C -/- and DKO mice were harvested for scRNA-seq. (L) Pan-cell-type UMAP embeddings with cells from both C -/- and DKO mice combined (n=10,000 cells per mouse). (M) Dot-plot of B-cell markers stratified by sub-population. Color represents average log fold expression.

Article Snippet: Human DLBCL cell lines SU-DHL-4 (CRL-2957), SU-DHL-5 (CRL-2958), and SU-DHL-10 (CRL-2963), Burkitt’s lymphoma cell lines Daudi and Ramos, as well as mantle cell lymphoma cell lines Z-138 and JeKo-1 were obtained from American Type Culture Collection (ATCC, Manassas, VA).

Techniques: Amplification, Expressing, Stable Transfection, Cell Culture

Journal: bioRxiv

Article Title: OSTM1 is a ubiquitin E3 ligase that suppresses B-cell malignancy by activating the cAMP/PKA/CREB pathway

doi: 10.64898/2026.01.23.701155

Figure Lengend Snippet: (A) Venn diagram showing overlap of B cell-specific CREB1 and CREBBP ChIP-seq targets. All targets identified in each dataset were used to determine overlap, and the top 1,500 common targets were selected for downstream analyses. (B) RNA expression data from the TCGA MDACC B-cell malignancies cohort. Heatmaps showing correlations between OSTM1, CREB1, or PDE3B mRNA levels and the top 1,500 CREB1/CREBBP co-occupied target genes identified in ( A ). (C) Venn diagrams showing overlap among genes significantly correlated with OSTM1, CREB1, or PDE3B within the top 1,500 CREB1/CREBBP targets. As OSTM1 negatively regulates PDE3B, genes positively correlated with OSTM1 and CREB1 expression and negatively correlated with PDE3B expression showed substantial overlap (78.2%). Conversely, genes negatively correlated with OSTM1 and CREB1 expression and positively correlated with PDE3B expression also overlapped significantly (66.8%). (D) CRISPR gene-effect scores from the CCLE database for OSTM1 and PDE3B across BCL lines, showing generally negative effects upon PDE3B silencing and positive effects upon OSTM1 silencing. (E) Pde3b was silenced by sgRNA in sg Ostm1 clone #3 Ba/F3 cells. PDE3B protein levels were determined by IB, and sg Ostm1/Pde3b double knockout (DKO) Ba/F3 cells were selected for subsequent experiments. (F) sgControl, sg Ostm1 , and DKO Ba/F3 cells were cutured in the presense or absence of IL3. Pde3b silencing reversed IL3-independence in sg Ostm1 cells. (G) GFP-expressing sg Ostm1 or DKO Ba/F3 cells were transplanted into nude mice via i.p. injection. Mice were harvested at the endpoint of the sg Ostm1 cohort. Spleens and livers were photographed and weighed. P values were calculated using Student’s t-test. GFP-positive tumor cells were detected only in sg Ostm1 recipients, but not in DKO recipients. (H) qRT-PCR in sgControl and sg Ostm1 Ba/F3 cells showing that Ostm1 silencing reduced expression of PKA/CREB/CREBBP target genes. (I) sgCtrl, sg Ostm1 , and DKO Ba/F3 cells were probed for phospho-PKA substrates and phospho-CREB (Ser133). (J) OSTM1 was silenced using two independent sgRNAs in SU-DHL-5 cells. Left: qPCR validation of OSTM1 knockout using on-target primers. Right: IB showing stablization of PDE3B and downregulation of cAMP/PKA signaling upon OSTM1 deletion. (K) OSTM1 was silenced in ARH-77 cells. IB of two clones shows increased PDE3B protein levles and decreased cAMP/PKA signaling upon OSTM1 silencing. (L) PDE3B-His was stably expressed in SU-DHL-10 cell line, which suppressed cAMP/PKA signaling. (M) OSTM1-Flag or OSTM1Δ31-Flag was stably expressed in OPM2 and RPMI-8226 cells. IB shows that OSTM1Δ31, but not the full-length OSTM1, promoted PDE3B degradation and enhanced cAMP/PKA signaling. (N) IB of whole-spleen lysates from indicated age-matched mice collected at the endpoints of O +/- ;C -/- or DKO cohorts. Phosphorylation levels of CREB and PKA substrates were generally reduced in the O -/- , O +/- C -/- , and DKO mice. (O) Bulk RNA-seq of purified splenic B cells from the indicated genotypes (as in ). Genes up-or down-regulated in DKO versus C -/- mice were intersected with the CREB1/CREBBP ChIP-seq targets identified in (A) . (P) Spleens from two-month-old C -/- and DKO mice were harvested, and 10,000 cells per mouse were analyzed by scRNA-seq. UMAP plots of B-cell subpopulations are shown by genotype. Bar graphs show the relative proportions of B-cell subsets. (Q) Genes down-regulated in DKO vs C -/- B cells, as identified by both bulk RNA-seq of splenic B cells and scRNA-seq of follicular B cells, were intersected with CREB1/CREBBP targets. Eight genes were commonly identified across all 4 datasets.

Article Snippet: Human DLBCL cell lines SU-DHL-4 (CRL-2957), SU-DHL-5 (CRL-2958), and SU-DHL-10 (CRL-2963), Burkitt’s lymphoma cell lines Daudi and Ramos, as well as mantle cell lymphoma cell lines Z-138 and JeKo-1 were obtained from American Type Culture Collection (ATCC, Manassas, VA).

Techniques: ChIP-sequencing, RNA Expression, Expressing, CRISPR, Double Knockout, Injection, Quantitative RT-PCR, Biomarker Discovery, Knock-Out, Clone Assay, Stable Transfection, Phospho-proteomics, RNA Sequencing, Purification

Journal: bioRxiv

Article Title: OSTM1 is a ubiquitin E3 ligase that suppresses B-cell malignancy by activating the cAMP/PKA/CREB pathway

doi: 10.64898/2026.01.23.701155

Figure Lengend Snippet: (A) Ostm1 was silenced in Ba/F3 cells using two independent sgRNAs. Successful knockout of Ostm1 was determined by genomic sequencing, which shows frame-shifting deletion, point mutations, and large-size deletion. (B) Human OSTM1-Flag was reconstituted into sg Ostm1 Ba/F3 cells, which led to the loss of IL3-independence of the sg Ostm1 cells. (C) OSTM1 was silenced in ARH-77 cells using sgRNA. Successful knockout of OSTM1 was determined by genomic sequencing. (C) Silencing OSTM1 in ARH-77 cells promoted cell proliferation. (D) OSTM1 was silenced in SU-DHL-5 cells with two sgRNAs. Successful silencing was achieved indicated by decreased mRNA levels, which led to increased cell proliferation. Statistical analysis in panels B , D , and E was done using multiple t-test, one per row. For panel E , one way ANOVA was used. **p<0.01; ***p<0.001.

Article Snippet: Human DLBCL cell lines SU-DHL-4 (CRL-2957), SU-DHL-5 (CRL-2958), and SU-DHL-10 (CRL-2963), Burkitt’s lymphoma cell lines Daudi and Ramos, as well as mantle cell lymphoma cell lines Z-138 and JeKo-1 were obtained from American Type Culture Collection (ATCC, Manassas, VA).

Techniques: Knock-Out, Genomic Sequencing

Journal: bioRxiv

Article Title: OSTM1 is a ubiquitin E3 ligase that suppresses B-cell malignancy by activating the cAMP/PKA/CREB pathway

doi: 10.64898/2026.01.23.701155

Figure Lengend Snippet: (A) sg Ostm1 and sgControl Ba/F3 cells were subjected to TMT-MS. Volcano plot (log₂ fold change vs. –log₁₀ p-value) was generated using VolcaNoseR. Dashed lines indicate significance cutoffs. Selected proteins involved in hematopoeitic function and differentiation are highlighted in red. (B) KEGG pathway enrichment analysis of proteins involved in sg Ostm1 Ba/F3 cells with-log10(FDR) used as the significance metric. (C) Venn diagram depicting the overlap between proteins enriched in sg Ostm1 cells identified by TMT-MS and OSTM1-interacting partners identified by BioID in Ba/F3 cells. The table shows BioID enrichment scores for Pde3b. (D and E) His-tagged PDE3B and Flag-tagged OSTM1 were co-transfected into HEK293T cells, in the presence or absence of MG132 (10 µM). Co-immunoprecipitation (Co-IP) was performed using anti-His (D) or anti-Flag (E) antibodies, followed by IB. (F) Ostm1 was silenced in Ba/F3 cells, and three independent cell clones were probed for Pde3b by IB. (G) qRT-PCR analysis of sg Ostm1 cell clones showing that Pde3b mRNA levels were not affected by Ostm1 silencing. (H) OSTM1-Flag was stably reconstituted in sg Ostm1 Ba/F3 cell clone #3, and Pde3b was probed by IB. (I) sgControl and sg Ostm1 Ba/F3 cells were treated with cycloheximide (CHX, 100 µg/ml) for the indicated hours. Pde3b was probled by IB and quantified using ImageJ. Pde3b half-life was calculated based on densitometry. Total ubiquitylated proteins were probed as an indicator of global protein turnover following CHX tratment. (J) sgControl and sg Ostm1 Ba/F3 cells were treated with MG132 (10 µM) or chloroquine (100 µM) for indicated hours, in the presence of CHX (100 µg/ml). Pde3b stability was determined by IB. Ubiquitin and Lc3b were probed to confirm the effectiveness of MG132 and CQ treatment. The Pde3b/Gapdh ratio is shown below the blots. (K) sgControl and sg Ostm1 Ba/F3 cells were treated with indicated concenrations of MG132 for 8 h, and Pde3b was detected by IB. (L) PDE3B-His was expressed in sgControl or sg Ostm1 Ba/F3 cells. IP with PDE3B antibody was performed, followed by IB with indicated antibodies. PDE3B-His ubiquitination was detected in sgControl cells and reduced in sg Ostm1 cells. (M) OSTM1-Flag and PDE3B-His were transfected into HEK293T cells, individually or together, along with His-ubiquitin. Cells were treated with MG132 (10 µM) for 8 h prior to IP with PDE3B antibody and IB. (N) OSTM1-Flag and PDE3B-His were expressed separately in HEK293T cells. Cell lysates were used individually or combined for in vitro ubiquitylation assays. OSTM1-Flag promoted both its auto-ubiquitylation and PDE3B ubiquitylation. (O) Spearman correlation analysis of OSTM1 and PDE3B protein abundance across BCL cell lines from different subtypes using CCLE proteomic data. (P) OSTM1-Flag was stably expressed in indicated BCL cell lines. Flag pull-down assays were performed, and interacting proteins were analyzed by IB. (Q and R) OSTM1 was silenced in SU-DHL-5 ( Q ) and ARH-77 ( R ) cell lines. Two clones per cell line were probed for PDE3B by IB. (S) sgControl and sg OSTM1 ARH-77 cells were treated with CHX (100 µg/ml). PDE3B was probed by IB, and its half-life was calculated based on ImageJ densitometric quantification.

Article Snippet: Human DLBCL cell lines SU-DHL-4 (CRL-2957), SU-DHL-5 (CRL-2958), and SU-DHL-10 (CRL-2963), Burkitt’s lymphoma cell lines Daudi and Ramos, as well as mantle cell lymphoma cell lines Z-138 and JeKo-1 were obtained from American Type Culture Collection (ATCC, Manassas, VA).

Techniques: Generated, Transfection, Immunoprecipitation, Co-Immunoprecipitation Assay, Clone Assay, Quantitative RT-PCR, Stable Transfection, Ubiquitin Proteomics, In Vitro, Quantitative Proteomics

Journal: bioRxiv

Article Title: OSTM1 is a ubiquitin E3 ligase that suppresses B-cell malignancy by activating the cAMP/PKA/CREB pathway

doi: 10.64898/2026.01.23.701155

Figure Lengend Snippet: (A) Venn diagram showing overlap of B cell-specific CREB1 and CREBBP ChIP-seq targets. All targets identified in each dataset were used to determine overlap, and the top 1,500 common targets were selected for downstream analyses. (B) RNA expression data from the TCGA MDACC B-cell malignancies cohort. Heatmaps showing correlations between OSTM1, CREB1, or PDE3B mRNA levels and the top 1,500 CREB1/CREBBP co-occupied target genes identified in ( A ). (C) Venn diagrams showing overlap among genes significantly correlated with OSTM1, CREB1, or PDE3B within the top 1,500 CREB1/CREBBP targets. As OSTM1 negatively regulates PDE3B, genes positively correlated with OSTM1 and CREB1 expression and negatively correlated with PDE3B expression showed substantial overlap (78.2%). Conversely, genes negatively correlated with OSTM1 and CREB1 expression and positively correlated with PDE3B expression also overlapped significantly (66.8%). (D) CRISPR gene-effect scores from the CCLE database for OSTM1 and PDE3B across BCL lines, showing generally negative effects upon PDE3B silencing and positive effects upon OSTM1 silencing. (E) Pde3b was silenced by sgRNA in sg Ostm1 clone #3 Ba/F3 cells. PDE3B protein levels were determined by IB, and sg Ostm1/Pde3b double knockout (DKO) Ba/F3 cells were selected for subsequent experiments. (F) sgControl, sg Ostm1 , and DKO Ba/F3 cells were cutured in the presense or absence of IL3. Pde3b silencing reversed IL3-independence in sg Ostm1 cells. (G) GFP-expressing sg Ostm1 or DKO Ba/F3 cells were transplanted into nude mice via i.p. injection. Mice were harvested at the endpoint of the sg Ostm1 cohort. Spleens and livers were photographed and weighed. P values were calculated using Student’s t-test. GFP-positive tumor cells were detected only in sg Ostm1 recipients, but not in DKO recipients. (H) qRT-PCR in sgControl and sg Ostm1 Ba/F3 cells showing that Ostm1 silencing reduced expression of PKA/CREB/CREBBP target genes. (I) sgCtrl, sg Ostm1 , and DKO Ba/F3 cells were probed for phospho-PKA substrates and phospho-CREB (Ser133). (J) OSTM1 was silenced using two independent sgRNAs in SU-DHL-5 cells. Left: qPCR validation of OSTM1 knockout using on-target primers. Right: IB showing stablization of PDE3B and downregulation of cAMP/PKA signaling upon OSTM1 deletion. (K) OSTM1 was silenced in ARH-77 cells. IB of two clones shows increased PDE3B protein levles and decreased cAMP/PKA signaling upon OSTM1 silencing. (L) PDE3B-His was stably expressed in SU-DHL-10 cell line, which suppressed cAMP/PKA signaling. (M) OSTM1-Flag or OSTM1Δ31-Flag was stably expressed in OPM2 and RPMI-8226 cells. IB shows that OSTM1Δ31, but not the full-length OSTM1, promoted PDE3B degradation and enhanced cAMP/PKA signaling. (N) IB of whole-spleen lysates from indicated age-matched mice collected at the endpoints of O +/- ;C -/- or DKO cohorts. Phosphorylation levels of CREB and PKA substrates were generally reduced in the O -/- , O +/- C -/- , and DKO mice. (O) Bulk RNA-seq of purified splenic B cells from the indicated genotypes (as in ). Genes up-or down-regulated in DKO versus C -/- mice were intersected with the CREB1/CREBBP ChIP-seq targets identified in (A) . (P) Spleens from two-month-old C -/- and DKO mice were harvested, and 10,000 cells per mouse were analyzed by scRNA-seq. UMAP plots of B-cell subpopulations are shown by genotype. Bar graphs show the relative proportions of B-cell subsets. (Q) Genes down-regulated in DKO vs C -/- B cells, as identified by both bulk RNA-seq of splenic B cells and scRNA-seq of follicular B cells, were intersected with CREB1/CREBBP targets. Eight genes were commonly identified across all 4 datasets.

Article Snippet: Human DLBCL cell lines SU-DHL-4 (CRL-2957), SU-DHL-5 (CRL-2958), and SU-DHL-10 (CRL-2963), Burkitt’s lymphoma cell lines Daudi and Ramos, as well as mantle cell lymphoma cell lines Z-138 and JeKo-1 were obtained from American Type Culture Collection (ATCC, Manassas, VA).

Techniques: ChIP-sequencing, RNA Expression, Expressing, CRISPR, Double Knockout, Injection, Quantitative RT-PCR, Biomarker Discovery, Knock-Out, Clone Assay, Stable Transfection, Phospho-proteomics, RNA Sequencing, Purification

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

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

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:

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

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

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