Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An outcome of low-grade B cell non-Hodgkins's lymphomas is the transformation to high-grade diffuse large B cell lymphomas (DLBL). To investigate the mechanisms of clonal evolution in the transformation to DLBL, we performed longitudinal molecular analyses of immunoglobulin (Ig), V(H)DJ(H) gene sequences expressed in cases of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and follicular lymphoma (FL) that transformed to DLBL. Among the neoplastic CLL and SLL cells and their respective high-grade transformants, there was no evidence for a clonotypic shift or acquired mutations in the expressed Ig V(H)DJ(H) gene segments, as further confirmed by a specific and sensitive PCR-single strand polymorphism analysis. In contrast, among the FL cells there was a high degree of intraclonal diversification with highly divergent V(H)DJ(H) gene sequences. Despite this intraclonal heterogeneity, the related DLBL expressed a collinear but unique V(H)DJ(H) gene sequence. The intraclonal genealogical tree for the FL case demonstrated that the DLBL emerged in association with unique V(H)DJ(H) gene mutational events. Among the intraclonal FL and related DLBL transformants, the nature and distribution of the Ig V(H)DJ(H) gene mutations were consistent with antigenic selection. Thus, clonal evolution in the transformation from low- to high-grade B cell lymphoma may involve distinct pathways which vary according to the cellular origin and the type of the progenitor B cell tumor.
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PMID:Clonal evolution of B cells in transformation from low- to high-grade lymphoma. 1022 93

The bcl-2 gene on chromosome 18 at q21 and the bcl-6 gene on chromosome 3 at q27 are both highly regulated during B-cell differentiation and show an inverse relationship of expression in the normal secondary lymphoid follicle. The objective of this study was to investigate the relationship between bcl-2 and bcl-6 protein expression and the relationship between protein expression and the corresponding chromosomal alterations in malignant lymphomas, including those associated with the germinal center. Expression of bcl-2 and bcl-6 proteins was studied in 55 cases of diffuse large B-cell lymphoma (DLBCL) and 21 cases of follicular lymphoma (FL), and the results correlated with the presence of t(14;18) and 3q27 abnormalities in a subset of 52 cases with cytogenetic analysis. These cases were selected to represent a spectrum of nodal and extranodal lymphomas, including those with and without a t(14;18). It was shown that the neoplastic cells in 71% of DLBCLs and 100% of FLs expressed bcl-6 protein. Expression of bcl-6 was seen more frequently in diffuse large B-cell lymphomas with large noncleaved morphology compared with immunoblastic morphology (82% v 27%, P = .0015), but failed to correlate with 3q27 abnormalities. Thirty-eight percent of cases with 3q27 abnormalities were bcl-6 protein negative, whereas 85% of cases without a 3q27 abnormalities were bcl-6 protein positive. Expression of bcl-2 protein was shown in 51% DLBCLs (nodal v extranodal, 71% v 30%, P = .012). bcl-2 protein was expressed in 89% of FLs with t(14;18), in contrast to 25% of FLs without t(14;18) (P = .016). In DLBCL and FL with t(14;18), the most common pattern of expression was bcl-2+/bcl-6+. In lymphomas without t(14;18), there was not an inverse relationship between bcl-2 and bcl-6 protein expression. In conclusion, these data suggest that mechanisms other than gene rearrangements can deregulate bcl-2 and bcl-6 expression in lymphomas, and there does not appear to be an inverse relationship between these two proteins as seen in the normal germinal center.
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PMID:Bcl-6 and Bcl-2 protein expression in diffuse large B-cell lymphoma and follicular lymphoma: correlation with 3q27 and 18q21 chromosomal abnormalities. 1041 99

The role of high-dose therapy and autologous stem cell transplantation in diffuse large B cell lymphoma (DLBCL) after transformation is controversial. We have retrospectively analyzed patients with chemosensitive disease and a history of follicular lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma who underwent high-dose chemoradiotherapy and bone marrow transplantation (BMT) with anti-B cell monoclonal antibody-purged autologous marrow for DLBCL. Between December 1982 and August 1997, 27 patients underwent autologous BMT using a uniform ablative regimen with cyclophosphamide, total-body irradiation, and bone marrow purging. All patients received multiple chemotherapy regimens before autologous BMT. At bone marrow (BM) harvest, only 44% of patients were in complete remission, and overt BM infiltration was present in 37%. After cyclophosphamide and total-body irradiation, no treatment-related deaths were seen. Eleven of the 27 patients relapsed, and four patients developed myelodysplasia/acute myelogenous leukemia. In seven patients in whom pathologic studies were available after relapse, the histology remained DLBCL. Twelve patients remained alive and in complete remission with a median follow-up of 36 months (range 10-132). The disease-free survival and overall survival are estimated to be 46% (90% confidence interval 28-64) and 58% (40-76) at 5 years, respectively. Patients whose disease underwent histologic transformation within 18 months of their initial diagnosis of indolent lymphoma had significantly better overall survival. Selected patients with histologic transformation, particularly those whose transformation occurs early in the course of their disease and who remain chemosensitive, may experience prolonged survival after autoBMT.
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PMID:Autologous bone marrow transplantation after histologic transformation of indolent B cell malignancies. 1046 6

Recombinant interferon-alfa (Intron A, Roferon-A) has been under investigation as a therapeutic agent for non-Hodgkin's lymphoma (NHL) for 25 years. It has antitumor efficacy in a number of histologic subtypes but has not been accepted as a clinically useful agent by the majority of oncologists/hematologists. A total of 10 prospective, randomized trials of interferon-alfa have been conducted in patients with follicular lymphoma. A survival benefit associated with interferon-alfa has been demonstrated in three of these trials, which used an anthracycline-based combination chemotherapy induction regimen, primarily in patients with bulky symptomatic disease. In this article, we review these trials, as well as the use of interferon-alfa in other NHL subtypes. Based on these data, we support the recommendation that interferon-alfa be added to an anthracycline-based induction regimen in the treatment of patients with clinically or histologically aggressive follicular lymphoma. This agent also appears to be effective in patients with diffuse large B-cell lymphoma and in patients with cutaneous T-cell lymphoma. Preliminary clinical data support the need for prospective, randomized phase III trials evaluating the role of interferon-alfa in these disorders.
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PMID:Role of interferon-alfa in NHL: still controversial? 1049 47

We have analyzed the immunoglobulin heavy chain (VH) gene variable regions (CDR2 and FW3) of 101 Japanese cases with peripheral B cell neoplasms. When all except one case with a deletion were graphed by frequency of replacement mutation, the 100 cases could be separated into two groups: 24 cases with zero, one and two mutations (germline or low frequency of somatic mutation); and 76 cases with three or more mutations (medium to high frequency of somatic mutation). While most mantle cell lymphoma cases (11/13) showed germline or low frequency of somatic mutation, all cases of mucosa-associated lymphoid tissue (MALT) lymphoma (11/11), follicular lymphoma (three of three cases), plasma cell myeloma (seven of seven cases) and most cases of diffuse large B cell lymphoma (DLBCL; 42/47) belonged to the latter group. These 76 cases, therefore, may be considered to show somatic hypermutation. More than half of chronic lymphocytic leukemia/small lymphocytic lymphoma cases (CLL/SLL; eight of 13) showed a hypermutated VH gene and the ratio of replacement mutation: silent mutation in CDR2 of CLL/SLL was considerably higher compared with DLBCL and MALT lymphoma, showing somatic hypermutation. When comparing VH gene type of B cell-CLL (B-CLL) among our series and those in the literature, more cases of CD5+ B-CLL in the Western literature have the VH5 and VH6 family types, while more cases in Japan are reported to have VH4 family. The occurrence of VH families in B-CLL between Japanese and Western people seems to be comparable.
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PMID:Analysis of the immunoglobulin heavy chain gene variable region of 101 cases with peripheral B cell neoplasms and B cell chronic lymphocytic leukemia in the japanese population. 1050 19

We have investigated the diagnostic value of fluorescence in situ hybridisation (FISH) to detect t(11;14) and trisomy 12 in 53 cases with a B cell leukaemia difficult to classify on clinical and laboratory grounds. These cases were initially diagnosed by morphology and immunophenotype and in 33 of them, on tissue histology, as follows: chronic lymphocytic leukaemia (CLL), 20, 18 of them with atypical features; B cell prolymphocytic leukaemia (B-PLL), two; mantle-cell lymphoma (MCL), 15; splenic lymphoma with villous lymphocytes (SLVL), five; lymphoplasmacytic lymphoma, six; follicular lymphoma, one and, four cases remained unclassifiable. FISH demonstrated BCL-1 rearrangement in the circulating cells from 15 cases classified as: MCL (10), atypical CLL (three) and B-PLL (two). A definitive diagnosis of MCL was made on review of the spleen histology in one out of the three atypical CLL with BCL-1 rearrangement. Trisomy 12 was detected in eight cases which included four atypical CLL, one typical CLL, two MCL and one unspecified B cell lymphoma by histology and morphology. One of the MCL had both trisomy 12 and BCL-1 rearrangement and the other was CD5+, CD23+ and had a CLL score of 3, suggesting the latter diagnosis. Our findings demonstrate that FISH analysis is useful to clarify the nature of the disease in patients presenting with a B cell leukaemia in which the diagnosis is difficult by conventional methods. FISH established with certainty the diagnosis of MCL by showing BCL-1 rearrangement in over two-thirds of cases in which this was suspected, including blastoid forms, and confirmed the diagnosis of most cases of atypical CLL.
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PMID:FISH analysis for BCL-1 rearrangements and trisomy 12 helps the diagnosis of atypical B cell leukaemias. 1055 44

The INK4A/ARF locus yields two tumor suppressors, p16INK4A and p14ARF, and is frequently deleted in human tumors. We studied their mRNA expressions in 41 hematopoietic cell lines and in 137 patients with hematological malignancies; we used a quantitative reverse transcription-PCR assay. Normal peripheral bloods, bone marrow and lymph nodes expressed little or undetectable p16INK4A and p14ARF mRNAs, which were readily detected in 12 and 17 of 41 cell lines, respectively. Patients with hematological malignancies frequently lacked p16INK4A expression (60/137) and lost p14ARF expression less frequently (19/137, 13.9%). Almost all patients without p14ARF expression lacked p16INK4A expression, which may correspond to deletions of the INK4A/ARF locus. Undetectable p16INK4A expression with p14ARF expression in 41 patients may correspond to p16INK4A promoter methylation or to normal expression status of the p16INK4A gene. All patients with follicular lymphoma (FL), myeloma or acute myeloid leukemia (AML) expressed p14ARF while nine of 23 patients with diffuse large B cell lymphoma (DLBCL) lost p14ARF expression. Patients with ALL, AML or blast crisis of chronic myelogenous leukemia expressed abundant p16INK4A mRNAs more frequently than patients with other diseases (12/33 vs 6/104, P < 0.01). Patients with FL and high p14ARF expression had a significantly shorter survival time while survival for patients with DLBCL and increased p14ARF expression tended to be longer. These observations indicate that p16INK4A and p14ARF expression is differentially affected among hemato- logical malignancies and that not only inactivation but also increased expression may have clinical significance.
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PMID:Expression of p16INK4A and p14ARF in hematological malignancies. 1055 50

Chemotaxis in leukocytes is mediated through binding of soluble chemokines to transmembrane G-protein coupled receptors. The chemokine receptor CXCR3 has been previously shown to be widely expressed on activated T cells and to mediate T-cell chemotaxis on binding to various ligands, including Mig, IP-10, and ITAC. By using immunohistochemical and flow cytometric analysis, we report that CXCR3 is also expressed on a subset of peripheral blood B cells and in distinct subtypes of B-cell lymphoma. CXCR3 immunohistochemical or flow cytometric expression was seen in 37 of 39 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (diffusely positive in 33 cases), whereas mantle cell lymphoma (30 cases), follicular lymphoma (27 cases), and small noncleaved cell lymphoma (8 cases) were negative in all but 2 cases. Strong CXCR3 expression was also seen in splenic marginal zone lymphoma (14 of 14 cases) and in the monocytoid and plasmacytic cells in extranodal marginal zone lymphoma (15 of 16 cases). This differential expression of CXCR3 in B-cell tumors contrasts with that of another B-cell-associated chemokine receptor, BLR1/CXCR5, which we show here is expressed on all types of B-cell lymphoma tested. We also report that the CXCR3 ligand, Mig, is coexpressed on tumor cells in many cases of CLL/SLL (10 of 13 cases examined) with Mig expression less frequently seen in other B-cell lymphoma subtypes. Coexpression of CXCR3 and its ligand, Mig, may be an important functional interaction in B-CLL, as well as a useful diagnostic marker for the differential diagnosis of small cell lymphomas. (Blood. 2000;95:627-632)
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PMID:The chemokine receptor CXCR3 is expressed in a subset of B-cell lymphomas and is a marker of B-cell chronic lymphocytic leukemia. 1062 72

Single cell studies aimed at clarifying the nature and clonality of Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin's disease (HD) have so far produced conflicting results. Using an improved single cell procedure, the HRS cells of 25 patients with nodular sclerosing HD lacking B- and T-cell antigens, with and without Epstein-Barr virus infection, were analyzed for the presence of immunoglobulin (Ig) gene rearrangements. One patient with HD developed follicular lymphoma 2 years later. Both lymphomas originated from a common precursor identified as a germinal center B cell. The data show that all but one of the investigated cases harbored rearranged Ig genes, which were clonal in all instances and carried a high load of somatic mutations. The Ig coding capacity was preserved in 18 of the 24 cases (75%) with rearrangements. However, expression of Ig messenger RNA was not detectable in the HRS cells with the exception of Ig kappa light chain expression in some tumor cells of 1 case. The lack of Ig gene transcription in HRS cells was confirmed by analyzing the HD cell lines L428 and KM-H2 in transient transfection experiments. An Ig promoter/enhancer reporter construct showed virtually no activity in these cells compared to 5 control B-cell lines. We conclude that (1) classical HD is a B-cell lymphoma in most instances, (2) HRS cells are clonal without any exception, (3) they are derived from germinal center B-cells that (4) mostly lack crippling mutations but (5) have consistently lost their Ig gene transcription ability, due to functional defects in the Ig gene regulatory elements. (Blood. 2000;95:1443-1450)
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PMID:Hodgkin and reed-sternberg cells represent an expansion of a single clone originating from a germinal center B-cell with functional immunoglobulin gene rearrangements but defective immunoglobulin transcription. 1066 23

Twenty-five patients with relapsed or refractory non-Hodgkin's lymphoma were treated by combination chemotherapy with irinotecan hydrochloride (CPT-11) and adriamycin (ADM): CPT-11, 25 mg/m2 on days 1 and 2; ADM, 40 mg/m2 on day 3. Nine (36%) of twenty-five patients achieved CR. Fairly good responses were seen in relapsed B-cell lymphomas (4 of 8 in diffuse large B-cell lymphoma and 2 of 2 in follicular lymphoma grade 1), and substantial responses in T-cell lymphomas (1 of 4 in peripheral T-cell lymphoma and 2 of 7 in adult T-cell leukemia/lymphoma). Leukopenia was frequent but tolerable, and diarrhea minimal. Combination chemotherapy with a reduced dose CPT-11 and ADM was useful in the treatment of relapsed non-Hodgkin's lymphoma.
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PMID:Combination chemotherapy with irinotecan and adriamycin for refractory and relapsed non-Hodgkin's lymphoma. 1069 Apr


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