Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The c-src proto-oncogene encodes a M(r) 60,000 phosphoprotein, pp60c-src, with tyrosine-specific protein kinase activity. We have used an immune complex protein kinase assay for pp60c-src to analyze a spectrum of B-cell neoplasms. pp60c-src activity was elevated in all five hairy cell leukemia specimens and in a number of the large cell and immunoblastic lymphomas; neoplasms representing later stages in B-cell development. pp60c-src activity was low in neoplastic cells which correspond to early and intermediate stages in B-cell development (acute and chronic lymphatic leukemia, lymphoblastic lymphoma, small lymphocytic lymphoma). The enhanced pp60c-src activity was associated with high levels of pp60c-src protein. However, increased expression of c-src was not associated with amplification or gross structural rearrangement of the c-src gene. This preliminary study demonstrates elevated levels of pp60c-src protein and tyrosine protein kinase activity in neoplasms corresponding to the later stages of B-cell ontogeny.
Leukemia 1993 Sep
PMID:Increased expression of the src proto-oncogene in hairy cell leukemia and a subgroup of B-cell lymphomas. 769 Apr 41

We describe an unusual case of small lymphocytic lymphoma with multiple prominent pseudofollicular proliferation centers in which immunohistochemistry reveals that the small cells are surface IgM kappa positive and the large pseudofollicular cells are surface IgA kappa positive. We further show by genomic DNA analysis that the tumor tissue contains two JH rearrangements, one Cmu rearrangement, one C alpha rearrangement, and a single C kappa rearrangement, strongly suggesting that the large cells within the proliferation centers have arisen from the small cells via a clonal heavy chain immunoglobulin isotype switch. Isotype switching in human lymphoma and leukemia appears to be an uncommon event. However, there are reports that strongly support isotype switching in pre-B-cell leukemia, Richter's syndrome, lymphoid blast crisis of chronic myelogenous leukemia, and multiple myeloma. To our knowledge, there have been no previous reports demonstrating isotype switching within the proliferation centers of small lymphocytic lymphoma. We present evidence of in vivo intratumoral isotype switching within the proliferation centers of a small lymphocytic lymphoma documented at the level of immunohistochemistry and DNA rearrangement.
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PMID:Clonal heavy chain isotype switching within the proliferation centers of a small lymphocytic lymphoma: implications regarding the origin of proliferation centers. 831 58

CD26 and CD40 ligand (CD40L) are surface molecules on human activated T lymphocytes that play a critical role in the regulation of lymphopoiesis. Both molecules are expressed on a restricted fraction of human T-cell non-Hodgkin's lymphomas (NHL)/leukemias; however, little is known about their functional and/or clinical significance in these disorders. In this study, the pattern of expression of CD40L was compared with that of the CD26 molecule. A series of 67 human T-cell NHL/leukemias and a panel of leukemia/lymphoma T-cell lines were evaluated by immunohistochemistry, flow cytometry, and RNA studies. The overall frequency of CD26+ and CD40L+ samples was rather similar (25/67 [37%] v 18/67 [27%]). However, the majority of CD26-expressing cases clustered in the lymphoblastic lymphomas (LBL)/T-acute lymphoblastic leukemias (ALL; 12/23) and CD30+ anaplastic large-cell (ALC) lymphomas (5/8), whereas CD40L+ lymphomas included a large fraction of mycosis fungoides (11/21 [52%]). CD26 and CD40L coexpression was found only in 2 myocosis fungoides cases and 1 small lymphocytic lymphoma. Thus, the expression of the two antigens was mutually exclusive in almost all T-cell lymphomas/leukemias. Accordingly, lymphoma cell lines expressed either one of the molecules or the relative amounts of CD26 and CD40L were inversely proportional. In contrast, reactive T lymphocytes from patients with non-neoplastic T-cell expansions and in vitro activated CD3+ or CD4+ normal T cells were found to coexpress CD40L and CD26. Results of a multivariate analysis showed that the expression of CD26 in T-cell LBL/ALL patients was associated to a worse outcome in terms of survival, as compared with patients with CD26- tumors (P < or = .0001). Based on our results, it can be concluded that, (1) as opposed to activated or reactive normal T cells, the expression of CD26 and of CD40L is mutually exclusive in human T-cell lymphomas/leukemias; (2) expression of CD26 is restricted to aggressive pathologic entities, such as T-cell LBL/ALL and T-cell CD30+ ALC lymphomas, whereas CD40L is expressed on slow progressing diseases such as mycosis fungoides; and (3) within the T-cell LBL/ALL group of tumors, CD26 may identify a subset of poor prognosis patients.
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PMID:The expression of CD26 and CD40 ligand is mutually exclusive in human T-cell non-Hodgkin's lymphomas/leukemias. 854 53

Three subtypes of small lymphocytic lymphoma were studied, namely B cell chronic lymphocytic leukemia (B-CLL), mantle cell lymphoma (MCL) and follicle center lymphoma (FCL). Agreement between tissue diagnosis, based on the proposal for a revised European-American classification of lymphoid neoplasms from the International Lymphoma Study Group, and the cytomorphological diagnosis on peripheral blood and/or bone marrow smears, using the proposals for the classification of chronic (mature) B and T lymphoid leukemias of the French-American-British Cooperative Group, was studied. Full agreement was found in 90% of the CLL and 82% of the FCL cases. In MCL cases, agreement was 65% including all cases classified as intermediate/mantle zone lymphoma according to FAB criteria. The incidence of bone marrow involvement detection in trephines compared to smears was equal in CLL (both 100%) and slightly higher in MCL (56 vs 48.5%); in FCL, however, trephine biopsies provided more reliable material (71 vs 35%).
Leukemia 1996 May
PMID:Small B cell NHL and their leukemic counterpart: differences in subtyping and assessment of leukemic spread. 865 82

Abnormal CCND1 expression is found in the majority of mantle cell lymphomas (MCL) and in a minority of other mature B cell malignancies. Its evaluation can therefore aid diagnostic classification, in conjunction with clinical, morphological, immunophenotypic and cytogenetic analysis. We describe a rapid slot-blot hybridization technique allowing quantitative assessment of CCND1 expression relative to beta-actin, with a sensitivity cut-off of approximately 10%. This allowed clear separation (P < 0.01) of CCND1 MCL (0.89 +/- 0.4; range 0.23-1.81; n = 25) from control samples (0.02 +/- 0.04; range 0-0.09; n = 22) on limited quantities of RNA (1-3.5 microg). Of nine samples in which a potential diagnosis of MCL lymphoma was based on morphological analysis of paraffin-embedded material, without adequate immunophenotype analysis, all were CCND1 negative and subsequent immunophenotype demonstrated features compatible with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) (CD5+, CD23+, FMC7-) in all cases tested. This study demonstrates the feasibility of slot-blot CCND1 quantification and the importance of the availability of cryopreserved material.
Leukemia 1998 Jan
PMID:Quantitative RNA slot-blot analysis of CCND1/cyclin D1 expression in suspected mantle cell lymphoma. 943 24

Expression of the CD5 antigen by neoplastic cells often is considered a diagnostic criterion for B-cell chronic lymphocytic leukemia (B-CLL). However, published series frequently include a number of CD5- cases. We studied the spectrum of CD5- B-cell lymphoproliferative disorders presenting with leukemia involvement and reassessed the prevalence of CD5- B-CLL. We immunophenotyped 192 cases of clonal, small lymphocytic, B-cell disorders involving peripheral blood or bone marrow. Of these, 41 CD5- cases were further analyzed, correlating the immunophenotypic findings with pathologic material and clinical data. Only 3 CD5- cases were classified as CD5- B-CLL. These 3 cases had features unusual for B-CLL, including bright surface immunoglobulin expression, bright CD20 expression, and absence of CD23 expression (2 cases) or Richter syndrome (1 case). The remainder of the CD5- cases consisted of hairy cell leukemia, hairy cell variant, prolymphocytic leukemia, follicular center cell lymphoma, lymphoplasmacytic lymphoma, splenic marginal zone lymphoma (SMZL), small lymphocytic lymphoma with marrow fibrosis, and lymphoma, not further classified. Eight cases remained unclassified, but some displayed features of SMZL. CD5- lymphoproliferative disorders of peripheral blood or bone marrow are unlikely to be CLL and often are classified more appropriately as non-Hodgkin lymphoma in the leukemia phase.
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PMID:CD5- small B-cell leukemias are rarely classifiable as chronic lymphocytic leukemia. 989 63

Unbalanced translocations involving chromosome arm 17p, where the TP53 tumor suppressor gene localizes, are rarely described in chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL), but recent use of molecular cytogenetic techniques have indicated a significant incidence of TP53 deletions, suggesting the involvement of chromosome 17p in these disorders. By conventional karyotype, we have identified unbalanced translocations involving 17p in 14 out of 123 (11%) CLL/SLL patients with clonal abnormalities. Cases were characterized by resistance to chemotherapy and a poor clinical outcome. The karyotypes presented a high incidence of complex rearrangements and 17p translocations were characterized by various partners. In 10 cases a centric fusion was assessed by fluorescent in situ hybridization (FISH) experiments using specific centromeric probes. The incidence of dicentric translocations in these series is therefore significantly higher than usually described, arising in up to 71% (10 out of 14 cases). In all cases, translocations led to a monosomy 17p and to a TP53 monoallelic deletion. The adverse clinical outcome confirms that structural abnormalities involving chromosome 17p are associated with disease progression in patients with chronic lymphoproliferative disorders.
Leukemia 1999 Mar
PMID:Translocations involving the short arm of chromosome 17 in chronic B-lymphoid disorders: frequent occurrence of dicentric rearrangements and possible association with adverse outcome. 1008 37

In B-chronic lymphoproliferative disorders (B-CLD) adhesion molecules (AM) have been investigated in order to explain the variable biologic behavior and dissemination patterns and to assess their contribution to the differential diagnosis and prognosis of these diseases. The main AM studied either by immunohistochemistry on lymph node sections or by flow cytometry in blood and bone marrow specimens are L-selectin, CD11a/CD18 (LFA-1), CD54 (ICAM-1), CD44 (HCAM), CD11c/CD18 (gp150/95), and CD49d/CD29 (VLA-4). Among B-CLD, hairy-cell leukemia (HCL) and follicular lymphoma (FL) show a uniform AM expression pattern. Thus, HCL is characterized by high CD54, CD44, VLA-4, CD11c, and CD18 and by low or absent CD11a and L-selectin, whereas FL confined to the lymph nodes is characterized by high CD11a, CD18, and CD54 expression. Diffuse growth and dissemination of FL is associated with alteration in the AM profile. Mantle-cell lymphoma (MCL) seems to be characterized by low or absent L-selectin and CD11c and high CD54 expression, especially compared with B-chronic lymphocytic leukemia (B-CLL). B-CLL is the most heterogeneous among all B-CLD with respect to AM expression. In general, low LFA-1 and CD54, high L-selectin and CD44, and variable CD11c characterize B-CLL. Cases with splenomegaly as their prominent feature bear high CD11a, CD18, CD29, and CD11c on the surface of the leukemic cells. Small lymphocytic lymphoma (SLL) shares the same AM phenotype with B-CLL, with the possible exception of LFA-1, which is strongly expressed on SLL cells. LFA-1 and CD54 are more frequently positive in lymphoplasmacytic lymphoma (LPL) as compared with B-CLL. Splenic lymphoma with villous lymphocytes differs from B-CLL by its high LFA-1, VLA-4, and CD54 and low L-selectin expression, whereas its high LFA-1 positivity can differentiate it from HCL. Surface and soluble AM have been investigated as possible prognostic markers in these diseases. Conflicting data exist concerning the prognostic significance of surface AM. However, high soluble (s)CD44 and CD54 levels in B-CLL and non-Hodgkin's lymphomas (NHL) are considered as adverse prognostic factors.
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PMID:Adhesion molecules in B-chronic lymphoproliferative disorders. 1031 87

To determine whether the expression levels of Bcl-2 family apoptotic regulators are correlated with the histopathological heterogeneity of B cell non-Hodgkin's lymphomas (NHL), we quantified their expression in malignant B cell populations isolated from 33 biopsy samples, including small lymphocytic lymphoma (SLL, n = 9), mantle cell lymphoma (MCL, n = 8), follicular lymphoma (FL, n = 8), and diffuse large cell lymphoma (DLCL, n = 8). Normal B cells purified from reactive lymph nodes and tonsil (n = 3) were used as controls. Cell lysates were analyzed by Western blotting, and signals quantified by densitometry. Expression of Bcl-2 and its homologues, Bcl-xL, Bcl-xS, Bax, Bad, Bak and Bag-1, was detected in all NHL cases, with wide variations between histological subtypes and within each subtype. Statistically significant differences were: (1) a higher level of Bad expression in DLCL compared to FL and MCL; (2) a lower level of Bak expression in FL compared to DLCL, SLL and MCL; and (3) a higher Bag-1 expression level in FL compared to SLL. When compared to NHL cells, normal B cells showed a higher level of Bax expression, and a lower level of Bcl-xL expression. Thus, quantitative analysis shows ubiquitous expression of Bcl-2 family proteins in normal and neoplastic B cells; the variations in expression levels may contribute to both the B-NHL clinicopathological diversity and the different apoptotic sensitivities of normal B cells vs B-NHL cells.
Leukemia 1999 Oct
PMID:Quantitative analysis detects ubiquitous expression of apoptotic regulators in B cell non-Hodgkin's lymphomas. 1051 56

Research in chronic lymphocytic leukemia (CLL) has undergone a resurgence of interest in the last decade. While it is obvious that most patients with CLL have typical mature B cells, a number of variants such as splenic lymphoma villous lymphocytes, mantle cell leukemia, and prolymphocytic leukemia need to be considered in the differential diagnosis. This can be established by immunophenotype studies and morphology. Cytogenetic abnormalities are emerging as being of interest, with abnormalities in chromosomes 11 and 17 having major prognostic significance. Immune disregulation is complicated in that along with hypergammaglobulinemia and T-cell dysfunction, the emergence of antibodies directed against hematopoietic cells causes autoimmune hemolytic anemia, neutropenia, and thrombocytopenia. A number of prognostic factors are emerging as being more influential in prognosis and stage, such as serum beta2-microglobulin and soluble CD23. Apoptosis dysregulation is a major feature of CLL, and while no clear pattern has emerged, abnormal levels of bcl2 are common in CLL and bcl2 to bax ratios are also commonly disturbed. Bcl1 levels are commonly increased. Treatment has changed radically. The purine analogs have been demonstrated to be the most active group of drugs in CLL. Combinations of purine analogs, such a fludarabine or 2-chlorodeoxyadenosine, with alkylating agents are emerging as new treatments. The most recent development has been the emergence of two monoclonal antibodies, rituximab (Rituxan; IDEC Pharmaceuticals, San Diego, CA, and Genentech, Inc, San Francisco, CA; directed against CD20) and Campath-1H (directed against CD52 in CLL). The activity of rituximab in lymphoma has been less prominent in small lymphocytic lymphoma (the lymphomatous counterpart of CLL) and this has led to dose escalation studies in CLL with a good level of response. Campath-1H is emerging as another major antibody with marked effect against disease, particularly in the blood and bone marrow. Autologous, allogeneic, and mini-transplant are also being explored extensively. The prognosis for patients with CLL is changing as these new treatments become available.
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PMID:Chronic lymphocytic leukemia. 1056 Oct 25


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