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)

Bone marrow lymphocyte subsets in normal and reactive states and in neoplastic diseases involving the marrow were investigated with a select panel of monoclonal antibodies reactive on routinely processed, paraffin-embedded trephine biopsy material. In all cases, the antibodies beta F1 and UCHL1 (CD45RO) stained virtually equal numbers of T cells (reactive and neoplastic), whereas antibody OPD4 stained only about one half of this number of T cells. Antibody L26 (CD20) stained B cells (reactive and neoplastic) in all specimens. The T-cell to B-cell ratio in the normal marrow was between 4:1 and 5:1, and a significant increase in T-cell numbers was observed in reactive and myelodysplastic states. A significant increase in B-cell numbers, however, was seen only in marrow infiltrated by B-cell lymphoma. Bone marrow exhibiting infiltrates of B-cell lymphoma, acute leukemia, or myeloproliferative disorders showed normal or decreased numbers of T cells. These findings show that antibodies UCHL1, beta F1, and L26 can be used to determine the numbers of B and T lymphocytes in paraffin-embedded, formalin-fixed bone marrow specimens and thus may help to distinguish reactive T lymphocytosis from B-cell lymphoma.
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PMID:Investigation of bone marrow lymphocyte subsets in normal, reactive, and neoplastic states using paraffin-embedded biopsy specimens. 843 87

We have studied 215 male patients (aged 45-97 years) whose sole cytogenetic abnormality was clonal loss of the Y chromosome in metaphase cells from unstimulated cultures. The patients comprised a control group with no evidence of hematologic disease and four disease case groups: 1) myelodysplastic syndrome (MDS), refractory anemia, refractory anemia with excess blasts (RAEB), RAEB in transformation, and chronic myelomonocytic leukemia; 2) acute myelogenous leukemia; 3) myeloproliferative disorder (MPD), chronic granulocytic leukemia, and polycythemia vera; and 4) B-cell lymphoma/leukemia. The frequency of cells with Y loss increased with age and was significantly greater in cases than in controls, but it was not correlated with survival or with prior therapy. The frequency of cases with a -Y clone was 6.3% of male karyotypes and represented 16.4% of all abnormal male cytogenetic reports. Much of the difference between cases and controls appears to be accounted for by a greater frequency of cases with > 75% Y loss. A value of 81% chromosome Y loss maximized the combined sensitivity (28%) and specificity (100%) for predicting disease status, but a 75% cutoff provided the best estimate of disease risk. Even in older males, if > 75% of metaphase cells are 45,X,-Y, they probably represent a disease-associated clonal population, and it is possible that the critical genetic change is not visible through the microscope. This observation is true for MDS, MPD, B-cell disease, and especially acute myelogenous leukemia. The prognostic association of Y chromosome loss for survival appears to be neutral or favorable. Genes Chromosomes Cancer 27:11-16, 2000.
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PMID:Clinical significance of Y chromosome loss in hematologic disease. 1056 81

We review the clinical, pathologic, and molecular genetic features of 3 splenic T-cell-rich B-cell lymphomas and discuss their differential diagnosis. All patients presented with symptomatic splenomegaly and underwent diagnostic/therapeutic splenectomy. Microscopically, the spleen in all cases showed a micronodular proliferation of lymphoid cells. A proportion of the nodules demonstrated central hyalinization or sclerosis. There was also an exuberant extramedullary hematopoiesis. On immunohistochemical stain, the nodules consisted predominantly of small T cells with scattered large atypical B cells. The clonal nature of the atypical B cells was confirmed by polymerase chain reaction assays for immunoglobulin heavy-chain gene rearrangement. In the H&E sections, the differential diagnoses included Hodgkin's lymphoma, follicular lymphoma, peripheral T-cell lymphoma, and nonneoplastic granulomatous process. The presence of exuberant extramedullary hematopoiesis also raised the possibility of a chronic myeloproliferative disorder. The combined morphologic, immunohistochemical, and molecular genetic data are essential for a correct diagnosis of splenic T-cell-rich B-cell lymphoma.
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PMID:T-cell-rich B-cell lymphoma presenting in the spleen: a clinicopathologic analysis of 3 cases. 1476 70

We report a case of BCR-ABL-negative atypical chronic myeloid leukemia (CML) with translocation t(4;22) (q12;q11.2) juxtaposing the breakpoint cluster region (BCR) and platelet-derived growth factor receptor-alpha (PDGFRA) genes. The patient was a 57-year-old man with a history of stage IV diffuse large B-cell lymphoma, status post-6 cycles of combination chemotherapy in 1999, who presented in August 2002 with enlarged lymph nodes, anemia, and marked leukocytosis (50 x 10(9) g/dL) consistent with a myeloproliferative disorder (MPD). A bone marrow biopsy showed granulocytic hyperplasia, neutrophilia, and mild eosinophilia. Initial cytogenetic evaluation by interphase FISH for BCR-ABL, to rule out a translocation 9;22, showed a variant signal pattern consistent with rearrangement of BCR at 22q11.2, but not ABL at 9q34. Analysis of the patient's cDNA by polymerase chain reaction (PCR) for BCR-ABL was negative. Cytogenetic analysis showed an abnormal karyotype with rearrangement of chromosomes 4 and 22. PCR amplification and subsequent sequence analysis demonstrated an in-frame 5'-BCR/3'-PDGFRA fusion in the patient's cDNA. PDGFRA encodes a receptor tyrosine kinase and shares structural and organizational homology with the KIT and CSf1R receptor genes. However, although the incidence of MPD involving translocations of PDGFRB has been well established, to our knowledge there are only two previous reports describing a BCR-PDGFRA fusion gene, in 3 patients diagnosed with atypical CML. Here, we report the molecular and cytogenetic characterization of a patient with BCR-PDGFRA-positive MPD who had a complete hematologic response after treatment with imatinib mesylate.
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PMID:Molecular and cytogenetic characterization of a novel translocation t(4;22) involving the breakpoint cluster region and platelet-derived growth factor receptor-alpha genes in a patient with atypical chronic myeloid leukemia. 1503 67

Reccurent chromosomal translocation t(4;14) (p16.3;q32.3) occurs in patients with multiple myeloma (MM) and is associated with ectopic overexpression of fibroblast growth factor receptor 3 (FGFR3) that sometimes may contain the activation mutations such as K650E thanatophoric dysplasia type II (TDII). Although there have been significant advances in therapy for MM including the use of proteasome inhibitors, t(4;14) MM has a particularly poor prognosis and most patients still die from complications related to their disease or therapy. One potential therapeutic strategy is to inhibit FGFR3 in those myeloma patients that overexpress the receptor tyrosine kinase due to chromosomal translocation. Here we evaluated PKC412, a small molecule tyrosine kinase inhibitor, for treatment of FGFR3-induced hematopoietic malignancies. PKC412 inhibited kinase activation and proliferation of hematopoietic Ba/F3 cells transformed by FGFR3 TDII or a TEL-FGFR3 fusion. Similar results were obtained in PKC412 inhibition of several different t(4;14)-positive human MM cell lines. Furthermore, treatment with PKC412 resulted in a statistically significant prolongation of survival in murine bone marrow transplant models of FGFR3 TDII-induced pre-B cell lymphoma, or a peripheral T-cell lymphoma associated TEL-FGFR3 fusion-induced myeloproliferative disease. These data indicate that PKC412 may be a useful molecularly targeted therapy for MM associated with overexpression of FGFR3, and perhaps other diseases associated with dysregulation of FGFR3 or related mutants.
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PMID:FGFR3 as a therapeutic target of the small molecule inhibitor PKC412 in hematopoietic malignancies. 1609 34

Signal transducer and activator of transcription (STAT) proteins are phosphorylated and activated by Janus kinases (JAKs). Recently, several groups identified a recurrent somatic point mutation constitutively activating the hematopoietic growth factor receptor-associated JAK2 tyrosine kinase in diverse chronic myeloid disorders - most commonly classic myeloproliferative disorders (MPD), especially polycythemia vera. We hypothesized that the JAK2 V617F mutation might also be present in samples from patients with acute myeloid leukemia (AML), especially erythroleukemia (AML-M6) or megakaryoblastic leukemia (AML-M7), where it might mimic erythropoietin or thrombopoietin signaling. First, we documented STAT3 activation by immunoblotting in AML-M6 and other AML subtypes. Immunoperoxidase staining confirmed phosphorylated STAT3 in malignant myeloblasts (21% of cases, including all AML-M3 samples tested). We then analyzed genomic DNA from 162 AML, 30 B-cell lymphoma, and 10 chronic lymphocytic leukemia (CLL) samples for JAK2 mutations, and assayed a subset for SOCS1 and FLT3 mutations. Janus kinase2 V617F was present in 13/162 AML samples (8%): 10/13 transformed MPD, and three apparent de novo AML (one of 12 AML-M6, one of 24 AML-M7, and one AML-M2 - all mixed clonality). FLT3 mutations were present in 5/32 (16%), while SOCS1 mutations were totally absent. Lymphoproliferative disorder samples were both JAK2 and SOCS1 wild type. Thus, while JAK2 V617F is uncommon in de novo AML and probably does not occur in lymphoid malignancy, unexplained STAT3 activation is common in AML. Janus kinase2 extrinsic regulators and other proteins in the JAK-STAT pathway should be interrogated to explain frequent STAT activation in AML.
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PMID:JAK2 V617F is a rare finding in de novo acute myeloid leukemia, but STAT3 activation is common and remains unexplained. 1659 6

Basophils play an important role in allergic inflammation and are pathologically related to hematological disturbances, such as iron deficiency anemia and myeloproliferative disorders; however, they are only rarely encountered in lymphoid malignancies. Here, we report the case of a 33-year-old man with a bulky mass of the small intestine, multiple paraaortic lymphoadenopathy, pleural effusion, and ascites, who was diagnosed as a case of de novo CD5+ diffuse large B cell lymphoma (DLBCL). This patient showed a marked elevation of the basophil count in the peripheral blood, which appeared to run in parallel with the tumor burden. High dose chemotherapy followed by autologous peripheral blood cell transplantation yielded complete remission, and the patient has remained disease free for 5 years. To the best of our knowledge, this is the first report of a case of de novo CD5+ DLBCL showing marked elevation of the PB basophil count.
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PMID:De novo CD5+ diffuse large B cell lymphoma with basophilia in the peripheral blood: successful treatment with autologous peripheral blood stem cell transplantation. 1701 91

Bone marrow (BM) biopsy is often performed early in the evaluation of patients with angioimmunoblastic T-cell lymphoma (AITL), and may be the first diagnostic tissue sample; yet the BM histopathology associated with this disease has not been well described. In this study, BM specimens from 13 patients with AITL were reviewed. Seven (54%) were involved by AITL, which was characterised by paratrabecular and interstitial polymorphous infiltrates containing cytologically atypical lymphocytes, histiocytes and eosinophils. The neoplastic cells were positive for CD10 and CXCL13 by immunohistochemistry in a subset of cases. As in lymph nodes, the lymphomatous infiltrate in some BMs contained numerous small or scattered large B cells, resembling either benign lymphoid aggregates or T cell rich large B cell lymphoma, respectively. Secondary haematological changes were frequent and presented independent of BM involvement by AITL; these included trilineage haematopoietic hyperplasia and plasmacytosis. When BM biopsy preceded the diagnosis of AITL, these secondary changes were misinterpreted as chronic myeloproliferative disease (n = 2), or plasma cell dyscrasia (n = 2). In two cases, these changes obscured the presence of BM involvement by AITL. The spectrum of BM findings in AITL patients is important to recognise for early and accurate diagnosis in this disease.
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PMID:Spectrum of bone marrow findings in patients with angioimmunoblastic T-cell lymphoma. 1748 86

Cytogenetic abnormalities of chromosome 12p involving the TEL/ETV6 gene are observed in a variety of hematopoietic neoplasms including acute leukemias, myelodysplastic syndromes, and myeloproliferative disorders. Karyotypic aberrations, including rearrangements, deletions, and amplifications of chromosome 12p, have been documented in B-cell non-Hodgkin lymphoma; however, rearrangements targeting TEL have rarely been reported. Here we describe a diffuse large B-cell lymphoma that had a complex karyotype including t(9;12)(q22;p13), which was confirmed by fluorescence in situ hybridization to represent rearrangement of TEL. Additional cytogenetic abnormalities included t(3;14)(q27;q32) involving the variant, alternative breakpoint region of the BCL6 gene and del(6)(q13q23), resulting in the loss of 1 allele of BLIMP1. This case reiterates the importance of correlating morphologic and phenotypic findings with the results of cytogenetic analysis to avoid errors in diagnosing hematologic neoplasms and highlights the rare association of B-cell non-Hodgkin lymphoma with aberrations of TEL.
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PMID:Diffuse large B-cell lymphoma with TEL/ETV6 translocation. 1899 13

Casitas B-cell lymphoma (Cbl)-family E3 ubiquitin ligases are negative regulators of tyrosine kinase signaling. Recent work has revealed a critical role of Cbl in the maintenance of hematopoietic stem cell (HSC) homeostasis, and mutations in CBL have been identified in myeloid malignancies. Here we show that, in contrast to Cbl or Cbl-b single-deficient mice, concurrent loss of Cbl and Cbl-b in the HSC compartment leads to an early-onset lethal myeloproliferative disease in mice. Cbl, Cbl-b double-deficient bone marrow cells are hypersensitive to cytokines, and show altered biochemical response to thrombopoietin. Thus, Cbl and Cbl-b play redundant but essential roles in HSC regulation, whose breakdown leads to hematological abnormalities that phenocopy crucial aspects of mutant Cbl-driven human myeloid malignancies.
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PMID:Rapidly fatal myeloproliferative disorders in mice with deletion of Casitas B-cell lymphoma (Cbl) and Cbl-b in hematopoietic stem cells. 2080 96


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