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Biomedical subjects

George Z Rassidakis

Publications and source records attributed to George Z Rassidakis.

At least 19 recordsLinked to original sources
PubMed2006

The t(14;19)(q32;q13)-positive small B-cell leukaemia: a clinicopathologic and cytogenetic study of seven cases.

The t(14;19)(q32;q13), involving the BCL3 locus at chromosome 19q13 and the immunoglobulin heavy chain gene at 14q32, is a rare recurrent cytogenetic abnormality identified in B-cell neoplasms, most of which have been classified as chronic lymphocytic leukaemia (CLL) in the literature. We describe the clinicopathological, immunophenotypic and cytogenetic findings in seven patients with B-cell neoplasms associated with t(14;19)(q32;q13). There were five men and two women, with a median age of 48 years (range 33-68). All had absolute lymphocytosis, six had lymphadenopathy, and one had splenomegaly. Lymphocytes in blood and bone marrow aspirate smears were predominantly small and cytologically atypical. Flow cytometric immunophenotyping showed an atypical immunophenotype with low CLL scores. The growth pattern in bone marrow biopsy specimens was interstitial to diffuse; immunohistochemical stains were positive for bcl3 and negative for cyclin D1. Lymph node biopsy specimens of two patients revealed total architectural effacement by neoplasm with proliferation centres. In addition to t(14;19), cytogenetic studies demonstrated trisomy 12 in five patients. These results suggest that B-cell neoplasms with the t(14;19)(q32;q13) present frequently as leukaemia composed of small B-lymphocytes and share many features with CLL. However, these neoplasms also differ from CLL cytologically and in their immunophenotype.

Adult↗
PubMed2006

Potential role of Jun activation domain-binding protein 1 as a negative regulator of p27kip1 in pancreatic adenocarcinoma.

Reduced expression of p27 has been associated with poor prognosis in most human cancers, including pancreatic adenocarcinoma. Jun activation domain-binding protein 1 (JAB1), an activator protein (AP-1) coactivator, previously implicated in p27 degradation, is overexpressed in various tumors and correlates with low p27 expression. We examined JAB1 and p27 in normal and neoplastic pancreatic tissues. Increased JAB1 expression was seen in pancreatic carcinoma samples but not in paired normal pancreatic tissues. Immunohistochemical analysis using tissue microarrays showed that JAB1 was overexpressed in all 32 (100%) pancreatic adenocarcinoma samples tested, predominantly nuclear in 23 (72%) samples and predominantly cytoplasmic in 9 (28%) tumors. When 10% was used as a cutoff for p27 positivity, p27 was expressed in 11 (34%) of tumors; however, p27 expression was localized in the nuclei of tumor cells in only 4 (13%) of the samples. Overexpression of the JAB1 in the pancreatic carcinoma cell lines Panc-1, Mia PaCa-2, and Panc-28 resulted in decreased p27 expression. Conversely, down-regulation of JAB1 by short interfering RNA substantially increased p27 expression and inhibited progression from G(1) to S phase of the cell cycle. Interestingly, JAB1-mediated p27 degradation was not impaired when S-phase kinase-interacting protein 2 (Skp2), an F-box protein required for the ubiquitination and consequent degradation of p27, was silenced. Thus, JAB1 may have an Skp2-independent p27 degradation mechanism in pancreatic cancer cells. These findings suggest that JAB1 overexpression is involved in the pathogenesis of pancreatic cancer through JAB1-mediated p27 degradation and that control of JAB1 expression is a novel therapeutic target in patients with pancreatic adenocarcinomas.

Adenocarcinoma↗
PubMed2006

Activation of mammalian target of rapamycin signaling pathway contributes to tumor cell survival in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma.

Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) frequently carries the t(2;5)(p23;q35) resulting in aberrant expression of chimeric nucleophosmin-ALK. Previously, nucleophosmin-ALK has been shown to activate phosphatidylinositol 3-kinase (PI3K) and its downstream effector, the serine/threonine kinase AKT. In this study, we hypothesized that the mammalian target of rapamycin (mTOR) pathway, which functions downstream of AKT, mediates the oncogenic effects of activated PI3K/AKT in ALK+ ALCL. Here, we provide evidence that mTOR signaling phosphoproteins, including mTOR, eukaryotic initiation factor 4E-binding protein-1, p70S6K, and ribosomal protein S6, are highly phosphorylated in ALK+ ALCL cell lines and tumors. We also show that AKT activation contributes to mTOR phosphorylation, at least in part, as forced expression of constitutively active AKT by myristoylated AKT adenovirus results in increased phosphorylation of mTOR and its downstream effectors. Conversely, inhibition of AKT expression or activity results in decreased mTOR phosphorylation. In addition, pharmacologic inhibition of PI3K/AKT down-regulates the activation of the mTOR signaling pathway. We also show that inhibition of mTOR with rapamycin, as well as silencing mTOR gene product expression using mTOR-specific small interfering RNA, decreased phosphorylation of mTOR signaling proteins and induced cell cycle arrest and apoptosis in ALK+ ALCL cells. Cell cycle arrest was associated with modulation of G(1)-S-phase regulators, including the cyclin-dependent kinase inhibitors p21(waf1) and p27(kip1). Apoptosis following inhibition of mTOR expression or function was associated with down-regulation of antiapoptotic proteins, including c-FLIP, MCL-1, and BCL-2. These findings suggest that the mTOR pathway contributes to nucleophosmin-ALK/PI3K/AKT-mediated tumorigenesis and that inhibition of mTOR represents a potential therapeutic strategy in ALK+ ALCL.

Anaplastic Lymphoma Kinase↗
PubMed2006

Intrinsic apoptotic pathway in anaplastic large cell lymphoma.

Anaplastic large cell lymphoma (ALCL) includes a subset of tumors that has abnormalities of chromosome 2p23, resulting in overexpression of anaplastic lymphoma kinase (ALK). Previous studies have reported differences in apoptotic rate and expression levels of apoptosis regulatory proteins between ALK+ and ALK- ALCL. In this study, we assessed for expression of the intrinsic apoptotic pathway proteins cytochrome c, apoptosis protease-activating factor 1, and procaspase 9 in 2 ALK+ ALCL cell lines and 42 ALCL tumors (17 ALK+, 25 ALK-). We used the Karpas 299 and SU-DHL-1 cell lines, and the inhibitors Z-LEHD-FMK (specific for caspase 9) and Boc-D-FMK (general caspase inhibitor) to investigate the role of caspase 9 activation in chemotherapy-induced apoptotic cell death. Caspase 9 activity was significantly increased in Karpas-299 and SU-DHL-1 cells after chemotherapy treatment, but remained as low as control levels with addition of either caspase inhibitor. Both caspase inhibitors rescued a substantial fraction of Karpas 299 and SU-DHL-1 cells from drug-induced cell death. In ALCL tumors, expression of cytochrome c, apoptosis protease-activating factor 1, and procaspase 9 was also assessed and correlated with apoptotic rate and activated caspase 3 levels. Cytochrome c was expressed in all 13 (100%) ALK+ and 18 (95%) of 19 ALK- ALCL tumors. Apoptosis protease-activating factor 1 was detected in 14 (88%) of 16 ALK+ and 19 (79%) of 24 ALK- ALCL tumors. Procaspase 9 was expressed in 5 (30%) of 17 ALK+ and 2 (8%) of 25 ALK- ALCL tumors (P = .09). In the entire study group (ALK+ and ALK- ALCL), procaspase 9 expression levels significantly correlated with apoptotic rate (P = .02) and activated caspase 3 levels (P = .05). This correlation could not be shown in the ALK+ or ALK- ALCL subgroups, presumably because of the small sample size. In conclusion, chemotherapy-induced cell death in ALK+ ALCL cells involves the intrinsic apoptotic pathway, and apoptosome function may be an important determinant of apoptosis in ALCL tumors.

Anaplastic Lymphoma Kinase↗
PubMed2006

53BP1 and p53 synergize to suppress genomic instability and lymphomagenesis.

p53-binding protein 1 (53BP1) participates in the cellular response to DNA double-stranded breaks where it associates with various DNA repair/cell cycle factors including the H2AX histone variant. Mice deficient for 53BP1 (53BP1(-/-)) are sensitive to ionizing radiation and immunodeficient because of impaired Ig heavy chain class switch recombination. Here we show that, as compared with p53(-/-) mice, 53BP1(-/-)/p53(-/-) animals more rapidly develop tumors, including T cell lymphomas and, at lower frequency, B lineage lymphomas, sarcomas, and teratomas. In addition, T cells from animals deficient for both 53BP1 and p53 (53BP1(-/-)/p53(-/-)) display elevated levels of genomic instability relative to T cells deficient for either 53BP1 or p53 alone. In contrast to p53(-/-) T cell lymphomas, which routinely display aneuploidy but not translocations, 53BP1(-/-)/p53(-/-) thymic lymphomas fall into two distinct cytogenetic categories, with many harboring clonal translocations (40%) and the remainder showing aneuploidy (60%). We propose that 53BP1, in the context of p53 deficiency, suppresses T cell lymphomagenesis through its roles in both cell-cycle checkpoints and double-stranded break repair.

Animals↗
PubMed2006

Expression of B cell-specific activator protein/PAX5 in acute myeloid leukemia with t(8;21)(q22;q22).

The blasts of acute myeloid leukemia (AML) with t(8;21)(q22;q22) frequently express the B-cell antigen CD19, which is regulated by B cell-specific activator protein (BSAP) encoded by the PAX5 gene, a protein important for B-cell lineage commitment and development. We assessed for BSAP expression in 28 AML cases with t(8;21) and 46 AML cases of other types. CD19 was expressed by 26 (93%) cases of AML with t(8;21) and 1 AML case (2%) without t(8;21). We also tested a subset of cases for the B-cell transcription factors Oct2 and OCA-B (BOB.1) and the B-cell antigens CD20, CD22, and CD79a. Immunostaining performed on bone marrow biopsy specimens demonstrated BSAP expression in all 28 AML cases with t(8;21): weak, 21; strong, 7. By contrast, BSAP was expressed weakly in only 1 AML case without t(8;21). Oct2 was expressed strongly in 12 of 16 AML cases with t(8;21) and 19 of 46 without t(8;21). OCA-B, CD20, CD22, or CD79a were negative in all cases assessed. These results indicate that silencing of PAX5 is not required for commitment to myeloid differentiation and that BSAP expression in AML is found mainly in cases with t(8;21).

Acute Disease↗
PubMed2006

Activation of mammalian target of rapamycin signaling promotes cell cycle progression and protects cells from apoptosis in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is characterized by the t(11;14) and cyclin D1 overexpression. However, additional molecular events are most likely required for oncogenesis, possibly through cell cycle and apoptosis deregulation. We hypothesized that mammalian target of rapamycin (mTOR) is activated in MCL and contributes to tumor proliferation and survival. In MCL cell lines, pharmacological inhibition of the phosphoinositide 3-kinase/AKT pathway was associated with decreased phosphorylation (activation) of mTOR and its downstream targets phosphorylated (p)-4E-BP1, p-p70S6 kinase, and p-ribosomal protein S6, resulting in apoptosis and cell cycle arrest. These changes were associated with down-regulation of cyclin D1 and the anti-apoptotic proteins cFLIP, BCL-XL, and MCL-1. Furthermore, silencing of mTOR expression using mTOR-specific short interfering RNA decreased phosphorylation of mTOR signaling proteins and induced cell cycle arrest and apoptosis. Silencing of eukaryotic initiation factor (eIF4E), a downstream effector of mTOR, recapitulated these results. We also assessed mTOR signaling in MCL tumors using immunohistochemical methods and a tissue microarray: 10 of 30 (33%) expressed Ser473p-AKT, 13 of 21 (62%) Ser2448p-mTOR, 22 of 22 (100%) p-p70S6K, and 5 of 20 (25%) p-ribosomal protein S6. Total eIF4E binding protein 1 and eukaryotic initiation factor 4E were expressed in 13 of 14 (93%) and 16 of 29 (55%) MCL tumors, respectively. These findings suggest that the mTOR signaling pathway is activated and may contribute to cell cycle progression and tumor cell survival in MCL.

Adaptor Proteins, Signal Transducing↗
PubMed2005

c-FLIP confers resistance to FAS-mediated apoptosis in anaplastic large-cell lymphoma.

We hypothesized that inhibition of the FAS-mediated apoptosis pathway by FLICE-like inhibitory protein (c-FLIP) may contribute to oncogenesis in ALK+ anaplastic large-cell lymphoma (ALCL). Treatment with increasing concentrations of CH-11 (CD95/FAS agonistic antibody) had no effect on cell viability of 2 ALK+ ALCL cell lines, Karpas 299 and SU-DHL1, each expressing high levels of c-FLIP. However, inhibition of endogenous c-FLIP expression by specific c-FLIP siRNA in Karpas 299 and SU-DHL1 cells treated with CH-11 resulted in FAS-mediated cell death associated with increased annexin V binding, apoptotic morphology, and cleavage of caspase-8. In 26 ALK+ ALCL tumors, assessed for expression of DISC-associated proteins, CD95/FAS and c-FLIP were commonly expressed, in 23 (92%) of 25 and 21 (91%) of 23 tumors, respectively. By contrast, CD95L/FASL was expressed in only 3 (12%) of 26 ALCL tumors, although it was strongly expressed by surrounding small reactive lymphocytes. Our findings suggest that overexpression of c-FLIP protects ALK+ ALCL cells from death-receptor-induced apoptosis and may contribute to ALCL pathogenesis.

Annexin A5↗
PubMed2005

Z-138 cell line was derived from a patient with blastoid variant mantle cell lymphoma.

The Z-138 cell line, reported in the journal in 1998, was derived from a patient who developed a leukemia initially classified as chronic lymphocytic leukemia in 1987. Splenectomy for massive involvement was required in 1998 and the neoplasm subsequently transformed to an aggressive, mature B-cell leukemia 2 years later. At time of transformation, the neoplasm had a complex karyotype, including the t(11;14)(q13;q32). In light of the extensive updates in lymphoma classification that have occurred since that time, we reviewed the slides of the patient's neoplasm. The initial peripheral blood and bone marrow aspirate smears and the spleen were involved by numerous small lymphocytes with mature chromatin. The last bone marrow specimen was involved by slightly larger, irregular lymphocytes with immature chromatin and a high mitotic rate. Immunohistochemical analysis performed on the spleen and last bone marrow for this report showed that the neoplastic cells over-expressed cyclin D1. According to the criteria of the current World Health Organization lymphoma classification, this neoplasm is best classified as mantle cell lymphoma, with blastoid transformation present in the terminal phase of disease.

Aged↗
PubMed2005

Differential expression of cyclin D3 in ALK+ and ALK- anaplastic large cell lymphoma.

As defined in the World Health Organization classification, anaplastic large cell lymphoma (ALCL) is a distinct type of non-Hodgkin lymphoma of T/null cell lineage, a subset of which is associated with translocations involving 2p23 resulting in expression of anaplastic lymphoma kinase (ALK). The most common translocation, the t(2;5)(p23;q35), results in expression of nucleophosmin (NPM)-ALK. NPM-ALK has been shown to activate signal transducer and activator of transcription (STAT) 3, a transcriptional regulator of cyclin D3. In this study, we assessed cyclin D3 expression in 2 ALK+ ALCL cell lines (Karpas 299 and SU-DHL1) and 1 ALK- ALCL cell line (Mac2A) by Western blot analysis. We also assessed cyclin D3 expression in 52 ALCL tumors (32 ALK+, 20 ALK-) by immunohistochemistry using tissue microarrays. These results were compared with phosphorylated (activated) STAT3 (pSTAT3) expression. Both ALK+ ALCL cell lines, but not the ALK- ALCL cell line, expressed cyclin D3 and pSTAT3. Cyclin D3 was expressed in 25 (78%) of 32 ALK+ ALCL tumors and in 4 (20%) of 20 ALK- ALCL tumors (P < .001, Fisher exact test ). In ALK+ ALCL tumors, the mean percentage of cyclin D3-positive tumor cells was 40.6% compared with 5.1% in ALK- ALCL tumors (P < .001, Mann-Whitney U test). The percentages of cyclin D3-positive and pSTAT3-positive tumor cells were positively correlated (Spearman R = 0.35, P = .036). We conclude that cyclin D3 is differentially expressed in ALK+ and ALK- ALCL and that high expression levels of cyclin D3 in ALK+ ALCL may be attributable to STAT3 activation.

Anaplastic Lymphoma Kinase↗
PubMed2005

Jak3 activation is significantly associated with ALK expression in anaplastic large cell lymphoma.

Janus kinase 3 (Jak3) is a tyrosine kinase that activates signal transducer and activator of transcription 3 (Stat3) in response to cytokine stimulation. Stat3 is an oncogene. In previous studies of anaplastic large cell lymphoma (ALCL), we showed that inhibition of Jak3 down-regulates activated/phosphorylated Stat3 (pStat3), decreases anaplastic lymphoma kinase (ALK) enzymatic activity, and induces cell-cycle arrest and apoptosis in ALK-positive ALCL. These findings implicate Jak3 as playing a significant role in the pathogenesis of ALK-positive ALCL; most likely via Stat3 and ALK activation. To assess this possibility, we used immunohistochemical staining to evaluate the frequency of expression of Jak3 and its activated/phosphorylated form (pJak3) in 48 systemic ALCL tumors included in a tissue microarray. pJak3 was detected in 17 (81%) of 21 ALK-positive tumors, compared with 3 (11%) of 27 ALK-negative tumors (P < .0001, Fisher exact test). pStat3 was present in 12 (86%) of 14 ALK-positive tumors and in 10 (40%) of 25 ALK-negative tumors assessed (P = .0078). Of 12 ALK-positive/pStat3-positive tumors, 8 (67%) expressed pJak3, but none of 10 ALK-negative/pStat3-positive tumors expressed pJak3. We conclude that Jak3 activation is predominantly restricted to ALK-positive ALCL tumors. Most likely, Jak3 collaborates with ALK in activating Stat3, leading to cell survival, cell-cycle progression, and tumor growth. In contrast, the mechanism of Stat3 activation in ALK-negative ALCL tumors appears to be independent of Jak3.

Adolescent↗
PubMed2005

Constitutive activation of JAK3/STAT3 in colon carcinoma tumors and cell lines: inhibition of JAK3/STAT3 signaling induces apoptosis and cell cycle arrest of colon carcinoma cells.

Signal transducer and activator of transcription 3 (STAT3) has oncogenic potential. The biological effects of STAT3 have not been studied extensively in the pathogenesis of colon cancer, nor has the role of Janus kinase 3 (JAK3), the physiological activator of STAT3, been evaluated. Here, we demonstrate that activated STAT3 (pSTAT3) and activated JAK3 (pJAK3) are expressed constitutively in two colon cancer cell lines, SW480 and HT29. To evaluate the significance of JAK3/STAT3 signaling, we inhibited JAK3 with AG490 and STAT3 with a dominant-negative construct. Inhibition of JAK3 down-regulated pSTAT3. The blockade of JAK3/STAT3 signaling significantly decreased viability of colon cancer cells due to apoptosis and cell-cycle arrest through down-regulation of Bcl-2, Bcl-X(L), Mcl-1, and cyclin D2 and up-regulation of p21(waf1/cip1) and p27(kip1). We also examined histological sections from 22 tumors from patients with stage II or stage IV colon cancer and found STAT3, JAK3, and their activated forms to be frequently expressed. Furthermore, quantitative reverse transcriptase-polymerase chain reaction identified JAK3 mRNA in colon cancer cell lines and primary tumors. Our findings illustrate the biological importance of JAK3/STAT3 activation in the oncogenesis of colon cancer and provide novel evidence that JAK3 is expressed and contributes to STAT3 activation in this malignant neoplasm.

Aged↗
PubMed2005

JunB expression is a common feature of CD30+ lymphomas and lymphomatoid papulosis.

JunB is a member of the Jun family of proteins that are components of the AP-1 transcription factor complex. AP-1 is involved in cell proliferation and apoptosis. Recent evidence suggests that Hodgkin and Reed-Sternberg cells overexpress JunB and that JunB facilitates constitutive CD30 expression by binding to an AP-1 site in the CD30 promoter. In this study we surveyed JunB expression in a variety of CD30+ lymphoma types including 42 cases of anaplastic large cell lymphoma, 36 classical Hodgkin lymphoma, 15 cutaneous anaplastic large cell lymphoma, and 11 CD30+ diffuse large B-cell lymphoma. In addition, seven cases of nodular lymphocyte-predominant Hodgkin lymphoma and 42 diffuse large B-cell lymphoma, known to be CD30-, were analyzed. JunB expression was assessed using tissue microarrays, immunohistochemistry and a monoclonal antibody specific for JunB. Expression of JunB was observed in 41 of 42 cases of anaplastic large cell lymphoma, including all 21 cases positive for anaplastic lymphoma kinase and 20 of 21 (95%) negative for anaplastic lymphoma kinase. JunB was also expressed in all cases of classical Hodgkin lymphoma, cutaneous anaplastic large cell lymphoma and CD30+ diffuse large B-cell lymphoma, and in lymphomatoid papulosis. By contrast, all nodular lymphocyte-predominant Hodgkin lymphomas and diffuse large B-cell lymphomas that were CD30- were also JunB-. We conclude that JunB is expressed in virtually all CD30+ lymphomas and is a potential target for experimental therapy in patients with these tumors.

Antibodies, Monoclonal↗
PubMed2005

Expression of heat-shock protein-90 in non-Hodgkin's lymphomas.

Heat-shock protein-90 (HSP90) inhibitors are currently being used in phase I clinical trials for treating patients with a variety of neoplasms including lymphomas. Using immunohistochemical methods, we assessed for HSP90 expression in 412 cases of non-Hodgkin's lymphoma. In B-cell lymphomas, HSP90 was moderately to strongly expressed in all cases of Burkitt's lymphoma (5/5, 100%), and in subsets of follicular lymphoma (17/28, 61%), diffuse large B-cell lymphoma (27/46, 59%), nodal marginal zone B-cell lymphoma (6/16, 38%), plasma cell neoplasms (14/39, 36%), small lymphocytic lymphoma/chronic lymphocytic leukemia (3/9, 33%), mantle cell lymphoma (12/38, 32%) and lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (3/10, 30%). HSP90 was weakly expressed in six of 14 (43%) cases of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. In T-cell lymphomas, HSP90 was moderately to strongly expressed in subsets of anaplastic large-cell lymphoma (14/24, 58%; 9/12 ALK+ and 5/12 ALK-), precursor-T-cell lymphoblastic leukemia/lymphoma (20/65, 31%), unspecified peripheral T-cell lymphoma (8/43, 23%) and angioimmunoblastic T-cell lymphoma (2/17, 12%). HSP90 was weakly expressed in seven of 58 (12%) cases of mycosis fungoides. We conclude that HSP90 is commonly expressed in a subset of many types of B- and T-cell lymphoma. These data suggest that many lymphoma types are suitable targets for modulation of HSP90 activity, and that HSP90 inhibitors are a potential investigational therapy for lymphoma patients.

Cell Line, Tumor↗
PubMed2005

Differential expression of WT1 gene product in non-Hodgkin lymphomas.

The tumor suppressor gene wt1 (Wilms tumor 1) encodes a zinc finger transcription factor reported to be expressed in many tumors, including mesotheliomas, carcinomas, and acute leukemias. However, WT1 expression in non-Hodgkin lymphomas (NHLs) has not been studied. The authors assessed for WT1 expression in six lymphoma/leukemia cell lines using Western blot methods after subcellular fractionation. We also assessed for WT1 expression in 167 NHLs using immunohistochemical methods. The B-cell NHLs analyzed were 18 diffuse large B-cell lymphomas, 13 marginal zone B-cell lymphomas, 9 small lymphocytic lymphomas, (DLBCLs), 8 follicular lymphomas, 6 mantle cell lymphomas, 5 Burkitt lymphomas, 3 lymphoplasmacytic lymphomas, and 2 B-cell lymphoblastic lymphomas. The T-cell NHLs analyzed were 43 anaplastic large cell lymphomas (ALCLs), 26 peripheral T-cell lymphomas unspecified, 13 angioimmunoblastic T-cell lymphomas, 6 cutaneous ALCLs, 6 cases of mycosis fungoides, 5 extranodal NK/T-cell lymphomas of nasal type, and 4 T-cell lymphoblastic lymphomas. WT1 levels were higher in cytoplasmic extracts than in nuclear extracts of the Karpas 299 and SU-DHL-1 lymphoma cell lines but were higher in nuclear extracts than in the cytoplasmic extracts of the Jurkat, HH, U-937, and K562 leukemia cell lines. In NHLs, WT1 was positive in 4 of 5 (80%) Burkitt lymphomas, 9 of 12 (75%) ALK-positive ALCLs, 3 of 6 (50%) lymphoblastic lymphomas (2 of 4 T-cell, 1 of 2 B-cell), 14 of 31 (45%) ALK-negative ALCLs, 6 of 18 (33%) DLBCLs, and 1 of 6 (17%) cutaneous ALCLs. WT1 was negative in all other NHLs tested. WT1 immunoreactivity was primarily cytoplasmic in all positive NHLs except T-cell lymphoblastic lymphoma. In conclusion, WT1 protein is frequently detected in the cytoplasm of a subset of high-grade NHLs.

B-Lymphocytes↗
PubMed2005

Expression of bcl-3 in chronic lymphocytic leukemia correlates with trisomy 12 and abnormalities of chromosome 19.

The bcl-3 gene at chromosome 19q13 encodes a member of the IkB family involved in regulating the nuclear factor kB pathway. Originally identified by its involvement in the t(14:19)(q32;q13), bcl-3 expression recently has been reported in 12% of non-Hodgkin lymphomas and 41% of Hodgkin lymphomas. Because the t(14;19) is detected most commonly in chronic lymphocytic leukemia (CLL), we assessed for bcl-3 expression using immunohistochemical analysis in 72 CLL cases with immunophenotypic and cytogenetic data. Of 72 CLL cases, 12 (17%) were bcl-3+. Expression of bcl-3 correlated with an atypical immunophenotype, defined using the World Health Organization scoring system. Expression also correlated with trisomy 12 and chromosome 19 abnormalities but was not limited to cases with the t(14:19)(q32;q13). Although the mechanism of bcl-3 expression is unclear, these results raise the possibility that bcl-3 may be involved in the pathogenesis of this subset of tumors and could be a potential target for investigational therapies.

Adult↗