Journal: The Journal of Clinical Investigation

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

doi: 10.1172/JCI134990

Figure Lengend Snippet: (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: Expressing, Quantitative RT-PCR, Transformation Assay, Positive Control, Control, Phospho-proteomics

Journal: The Journal of Clinical Investigation

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

doi: 10.1172/JCI134990

Figure Lengend Snippet: (A) We used publicly available methylation data sets (30) generated from different developmental 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-positive 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 similarity 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: Methylation, Generated, Expressing, Cell Differentiation, Transformation Assay, Derivative Assay

Journal: The Journal of Clinical Investigation

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

doi: 10.1172/JCI134990

Figure Lengend Snippet: 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: The Journal of Clinical Investigation

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

doi: 10.1172/JCI134990

Figure Lengend Snippet: 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+ immature 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: Expressing, Isolation, Ex Vivo, In Vivo, Gene Expression, RNA Sequencing, Transformation Assay, Derivative Assay

Journal: The Journal of Clinical Investigation

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

doi: 10.1172/JCI134990

Figure Lengend Snippet: (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 preactivated 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 crizotinib 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: Quantitative RT-PCR, Derivative Assay, Expressing, Transfection, Negative Control, Western Blot, Control

Journal:

Article Title: Overexpression of Mcl-1 in Anaplastic Large Cell Lymphoma Cell Lines and Tumors

doi:

Figure Lengend Snippet: a: A representative case of ALK+ ALCL with strong Mcl-1 expression in most tumor cells. (immunoperoxidase with hematoxylin counterstain, ×400). b: Double histogram demonstrating the distribution of ALK+ (black) and ALK− (gray) systemic ALCL tumors according to the percentage of Mcl-1-positive tumor cells. The x axis represents the percentage of Mcl-1-positive tumor cells and the y axis shows the percentage of tumors.

Article Snippet: 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).

Techniques: Expressing

Journal: Scientific Reports

Article Title: The c-Jun and JunB transcription factors facilitate the transit of classical Hodgkin lymphoma tumour cells through G 1

doi: 10.1038/s41598-018-34199-9

Figure Lengend Snippet: shRNA–mediated knock-down of JunB in ALK+ ALCL cell lines results in reduced proliferation. Western blots showing JunB levels ( A – C ) and growth curves ( D – F ) of the indicated cell lines expressing either control or JunB shRNA. Growth curves represent five experiments from three infections ( D ), five experiments from five infections ( E ), and three experiments from one infection ( F ). Note: JunB#6 and JunB#1 shRNAs overlap in their seed sequence and are not distinct. BrdU/7-AAD double staining of Karpas 299 ( G ) or SUP-M2 ( H ) cells expressing control or JunB shRNA. Results represent the average and standard deviation of three independent experiments from three infections for Karpas 299 cells, and eight independent experiments from six infections for SUP-M2 cells. ( I ) Bar graph showing the percentage of cells in S phase (% BrdU positive cells) observed when control shRNA or JunB shRNA–expressing Karpas 299 cells were transfected with plasmids expressing either EGFP-P2A or EGFP-P2A-FLAG-JunB. The results represent the average and standard deviation of four independent experiments. ( J ) Approximate doubling times and time spent in each stage of the cell cycle was determined for Karpas 299 and SUP-M2 cells expressing control or JunB shRNA. ( K ) Representative flow cytometry data and summary of Ki-67 expression within the G 0 /G 1 population of SUP-M2 cells expressing control or JunB shRNA. The summary represents the average and standard deviation of three independent experiments from two separate infections. P values were obtained by performing independent, two-tailed t tests comparing the JunB knock-down to control shRNA–expressing cells ( D – F and K ) or between JunB knock-down cells with or without JunB cDNA ( I ). ANOVA with Tukey’s post hoc test was performed in ( I ). * P < 0.05, ** P < 0.01, *** P < 0.001. Molecular mass markers (in kDa) are indicated to the left of western blots.

Article Snippet: The UCONN-L2 ALK+ ALCL cell line was obtained from Dr. Raymond Lai (University of Alberta; Edmonton, AB, Canada).

Techniques: shRNA, Knockdown, Western Blot, Expressing, Control, Infection, Sequencing, Double Staining, Standard Deviation, Transfection, Flow Cytometry, Two Tailed Test

Journal: Scientific Reports

Article Title: The c-Jun and JunB transcription factors facilitate the transit of classical Hodgkin lymphoma tumour cells through G 1

doi: 10.1038/s41598-018-34199-9

Figure Lengend Snippet: shRNA–mediated knock-down of c-Jun in ALK+ ALCL cell lines does not impair proliferation. Western blots showing c-Jun levels ( A , C , and E ) and growth curves ( B , D , and F ) of the indicated cell lines expressing either control or c-Jun shRNA. Growth curves represent four experiments from four infections (c-Jun#1) and five experiments from three experiments (c-Jun#5) ( B ), three experiments from three infections ( D ), and three experiments from one infection ( F ). Although, not included in the growth curve shown, c-Jun knock-down in UCONN-L2 had no effect on proliferation in other infections. ( G ) The percentage of cells in each stage of the cell cycle was measured by BrdU/7-AAD double staining for SUP-M2 cells expressing either control or c-Jun shRNA. The results represent three experiments from three infections. No statistically significant differences in growth rate or cell cycle distribution were observed between any c-Jun knock-down cells and respective control shRNA–expressing cells. Molecular mass markers (in kDa) are indicated to the left of western blots.

Article Snippet: The UCONN-L2 ALK+ ALCL cell line was obtained from Dr. Raymond Lai (University of Alberta; Edmonton, AB, Canada).

Techniques: shRNA, Knockdown, Western Blot, Expressing, Control, Infection, Double Staining

Journal: Oncotarget

Article Title: The ALK inhibitor ASP3026 eradicates NPM-ALK + T-cell anaplastic large-cell lymphoma in vitro and in a systemic xenograft lymphoma model

doi:

Figure Lengend Snippet: (A) At 48 h, ASP3026 induced concentration-dependent decreases in the viability of NPM-ALK + ALCL cells, as measured by MTS assay. These effects were not detected in T lymphocytes, and the decrease in the viability of NPM-ALK + ALCL cells was statistically significant compared to T lymphocytes (at 0.1 μM concentration: P < 0.05 in SU-DHL-1, P < 0.01 in Karpas 299, P = 0.0001 in SR-786, P < 0.0001 in SUP-M2, P > 0.05 in DEL [not significant]; at 0.5 μM concentration: P < 0.0001 in all cell lines except DEL where P > 0.05 [not significant]; at ≥ 1.0 μM concentration: P < 0.0001 in all cell lines). (B) The effects of ASP3026 on cell viability were more pronounced at 72 h after treatment (at ≥ 0.5 μM: P < 0.0001 in all cell lines compared with T lymphocytes). (C) Treatment of the NPM-ALK + ALCL cells Karpas 299, SR-786, and SU-DHL-1 with ASP3026 for 48 h was associated with significant concentration-dependent increases in apoptotic cell death, as measured by flow cytometry after cellular staining with annexin V/PI (*: P < 0.0001 compared with vehicle-treated control cells). (D) Morphologic features associated with apoptotic cell death, including cellular shrinkage and nuclear condensation and fragmentation, are shown in Karpas 299, SR-786 and SU-DHL-1 cells after treatment with ASP3026 for 48 h (red arrowheads). (E) ASP3026 also decreased the proliferation of NPM-ALK + ALCL cells as measured by BrdU assay (*: P < 0.05, **: P < 0.0001 compared with control cells treated with vehicle). (F) Moreover, ASP3026 abrogates anchorage-independent colony formation of NPM-ALK + ALCL cells in methylcellulose (*: P < 0.05, **: P < 0.01, ***: P < 0.001 compared with vehicle-treated control cells). (G) Representative cultures illustrating the marked decrease in the number of NPM-ALK + ALCL cell colonies at 5 days after treatment with ASP3026 for 48 h. Results are shown as means ± SE of at least 3 consistent experiments.

Article Snippet: The NPM-ALK + T-cell ALCL cell lines Karpas 299, SU-DHL-1, SUP-M2, SR-786, and DEL were purchased from DSMZ (Braunschweig, Germany).

Techniques: Concentration Assay, MTS Assay, Flow Cytometry, Staining, Control, BrdU Staining

Journal: Oncotarget

Article Title: The ALK inhibitor ASP3026 eradicates NPM-ALK + T-cell anaplastic large-cell lymphoma in vitro and in a systemic xenograft lymphoma model

doi:

Figure Lengend Snippet: (A) C.B-17 SCID mice were randomized into the 4 illustrated treatment groups at week 3 after intravenous injection of Karpas 299 cells permanently expressing firefly luciferase. “R” denotes relapse after ASP3026 discontinuation. (B) Mice developed NPM-ALK + ALCL tumors within approximately 3 weeks after injection, and were monitored weekly using bioluminescence imaging. The intensity of the signal is indicated by color (blue: low; green: intermediate; red: high tumor burden). Mice uninterruptedly treated with ASP3026 (examples shown in lanes 1 & 2) underwent complete remission with no relapse until study termination at week 13. Administration of ASP3026 was interrupted in 5 mice (examples in lanes 3-6) for 4 weeks. Notably, ALCL relapsed as early as 1 week after discontinuation of ASP3026. Two mice (lanes 3 & 4) had to be euthanized before the study period ended because of relapsed NPM-ALK + ALCL with extensive tumor burden. At week 9, ASP3026 was re-administered in the other 3 mice (2 shown in lanes 5 & 6), and the NPM-ALK + ALCL tumors substantially regressed, and the mice survived until termination of the study. (C) Bioluminescence imaging highlights the NPM-ALK + ALCL tumors in control and ASP3026-treated mice (upper panels). Mice were injected intraperitoneally by the firefly luciferase prosubstrate VivoGlo Caspase-3/7 and bioluminescence imaging was performed. Tumors in control mice treated only with vehicle failed to demonstrate significant apoptosis signals (left lower panel). In contrast, intense signals consistent with marked in vivo lymphoma cell apoptosis were detected in mice treated with ASP3026 (right lower panel). (D) Examples of control mice showing lymphoma (red arrows) in cervical lymph nodes (a, exterior; b, dissected); inguinal lymph nodes (c, d); mesenteric lymph nodes (e); and axillary lymph nodes (f). Example of cervical lymph nodes is shown in a mouse treated interruptedly with ASP3026 (group I). After relapse, this mouse received ASP3026, survived, and was euthanized at the end of the study. A small cervical lymph node (red arrow) was detected at necropsy (g). This lymph node was processed and microscopically examined as shown in Figure , lower panel. Example of cervical lymph nodes is shown after relapse in a mouse treated interruptedly with ASP3026. The lymph nodes comprised large, bulky tumor masses (red arrows) (h). (E) Histologic sections from cervical lymph node obtained from a control mouse treated with vehicle show effacement of the normal nodal architecture by solid sheets of lymphoma cells (H&E staining; original magnification: ×100). Higher magnification shows large cells with abundant cytoplasm, vesicular nuclei, and high mitotic rate with atypical mitotic figures [red arrowheads] (H&E; ×400). Immunohistochemical staining shows cytoplasmic and nuclear localization of NPM-ALK protein in the solid sheets of the lymphoma cells. Ki-67 is expressed in the vast majority of the lymphoma cells that diffusely infiltrate the lymph node. In addition, pSTAT3 Y705 and pIGF-IR Y1161 are highly expressed in almost all of the lymphoma cells. Also shown are histologic sections from a small post-treatment cervical lymph node collected at necropsy from a mouse treated with ASP3026 after relapse (I group, illustrated in Figure , panel g). H&E staining shows small nests of ALCL cells separated by thick stromal tissue strands (×100). Higher magnification of the same lymph node further illustrates the small clusters of lymphoma cells with rare mitotic figures [yellow arrows] separated by thick stromal strands that include fibroblasts, small blood vessels, and admixed inflammatory cells [red arrows] (×400). Although NPM-ALK and Ki-67 were identified in residual ALCL cells, the numbers of these cells were much less pronounced after treatment. The expressions of pSTAT3 and pIGF-IR are substantially reduced in the lymph node sections from the ASP3026-treated mouse. Immunohistochemical staining photomicrographs are shown at an original magnification of ×400. (F) Control mice at week 3 (top left) and weeks 6-7 (bottom left) show remarkable progression of systemic NPM-ALK + ALCL. Examples of mice from the CHOP-treatment group with NPM-ALK + ALCL established at week 3 (top right). Although CHOP initially suppressed NPM-ALK + ALCL tumor growth, lymphoma relapsed as illustrated at week 9 and the mice had to be euthanized because of heavy tumor burden (bottom right).

Article Snippet: The NPM-ALK + T-cell ALCL cell lines Karpas 299, SU-DHL-1, SUP-M2, SR-786, and DEL were purchased from DSMZ (Braunschweig, Germany).

Techniques: Injection, Expressing, Luciferase, Imaging, Control, In Vivo, Staining, Immunohistochemical staining

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

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: Fig. 1 | WASP and WIP are selectively down-regulated in ALCL. 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 versus AITL, ****P = 5.85 × 10−6; ALK+ ALCL versus PTCL-NOS, ****P = 6.08 × 10−12; ALK+ ALCL versus ALK– ALCL, **P = 0.0075; significance was determined by unpaired, two-tailed Student’s t-test). TNFRS8 (CD30) is strongly expressed in ALK– and ALK+ ALCL but not in other TCL subtypes. b, Representative H&E staining and immunohistochemistry stainings performed with the indicated antibody on human T cell lymphoma subtypes. The number of human T cell lymphoma samples analyzed is reported in Fig. 1c. WASP antibody was validated in formalin-fixed samples on samples with inducible WASP expression (Supplementary Fig. 7f). WIP antibody cross reacts with mouse WIP and was validated on WIP knockout cells (Supplementary Fig. 1b). Scale bar, 100 μm. Insets: high-magnification images. c, WASP and WIP expression in human T cell lymphoma subtypes. AITL, n = 20; PTCL-NOS, n = 20; ALK– ALCL, n = 29; ALK+ ALCL, n = 43 for WASP and n = 31 for WIP; other TCL are natural killer (NK)/T cell lymphoma, nasal-type, n = 3 and hepatosplenic γδ T cell lymphoma, n = 3. The number of patient samples is indicated for each lymphoma subtype. WASP and WIP expressions were quantified by immunostaining. Normal expression, expression equal to surrounding reactive T cells; low expression, decreased expression compared to surrounding reactive T cells; and no expression, absence of expression in lymphoma cells.

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, Staining, Immunohistochemistry, Expressing, Knock-Out, Immunostaining