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)

We have investigated the precise distribution of human B-lymphocyte subpopulations (CD5+ B lymphocyte, Leu-8+ lymphocyte, immunoglobulin D (IgD)+ lymphocyte, alkaline phosphatase (ALPase)+ B lymphocyte and bcl-2 protein+ B lymphocyte) within the mantle zones (MZs) and phenotypic characterization of human CD5+ B lymphocytes using immunohistochemical techniques and flow cytometric analysis. IgD+ lymphocytes and ALPase B lymphocytes were confined to the inner layer and outer layer of the MZs of secondary follicles, respectively. CD5+ B lymphocytes and Leu-8+ B lymphocytes were mostly located in the inner layer of the MZs. Bcl-2 protein+ B lymphocytes were seen throughout the MZs. The precise distribution pattern of human B-lymphocyte subpopulations may help further understanding of the histogenesis and features of B-cell lymphomas, particularly mantle cell-derived lymphomas as well as the B-cell differentiation pathway. A minor population of CD5+ B lymphocytes expressed IgD. Almost all the CD5+ lymphocytes did not express ALPase. The data support the fact that CD5+ B lymphocytes are located more in the inner layer than in the outer layer of the MZs. Leu-8 and bcl-2 protein were detected in a large population of CD5+ B lymphocytes. In addition, Ki-67 antigen was not expressed on the CD5+ B lymphocytes. The data suggest that human CD5+ B lymphocytes may be long-living and resting (G0 and G1a stage) cells possessing the capability of continuously recirculating between blood and lymph nodes to participate in some immune responses. Moreover, Leu-8 and CD44 were detected in the majority of CD5+ B lymphocytes but intercellular adhesion molecule-1 (ICAM-1) and very late antigen-4 (VLA-4) were detected in the minority. The data may account for a high percentage of Leu-8 and CD44 expression and a low percentage of ICAM-1 and VLA-4 expression on B-chronic lymphocytic leukemia (B-CLL), which is considered to be a neoplastic counterpart of normal CD5+ B lymphocyte.
Leukemia 1994 Jun
PMID:Phenotypic characterization of human B-lymphocyte subpopulations, particularly human CD5+ B-lymphocyte subpopulation within the mantle zones of secondary follicles. 751 26

In human leukemic cells clinically relevant concentrations of taxol have been demonstrated to induce the biochemical and morphologic hallmarks of apoptosis (Leukemia 1993;7:563-568). Since overexpression of the bcl-2 gene has been reported to retard apoptosis due to a variety of anticancer agents, we examined and compared taxol-induced intracellular microtubular bundling and apoptosis in pre-B human leukemia 697 cells and their counterparts which have been transfected with and overexpress cDNA derived from the bcl-2 gene. Treatment with 0.1 or 1.0 mumol/l taxol for 24 h resulted in internucleosomal DNA fragmentation and morphologic features of apoptosis in 697 cells, but not in 697/BCL-2 cells. However, indirect immunofluorescent staining with anti-tubulin antibody revealed that taxol treatment produces stable microtubule bundles resistant to calcium-mediated disassembly in 697, as well as 697/BCL-2 cells. In addition, taxol-induced microtubule bundling was associated with a marked accumulation of the two cell types in the G2/M phase of the cell cycle. Following exposure to taxol, when 697 cells were washed and kept in drug-free medium, they showed rapid onset of apoptosis followed by loss of cell viability and a decline in cell numbers. In contrast, identically treated 697/BCL-2 cells kept in drug-free medium remained in a growth arrested state, but showed little evidence of apoptosis for up to 4 days. They eventually demonstrated features of apoptotic cell death and loss of viability between 5 and 7 days. This was not accompanied by a decrease in p26BCL-2 levels. Anti-phosphotyrosine or anti-MAP kinase immunoblot analyses of proteins isolated from taxol-treated 697 and 697/BCL-2 cells failed to show any difference in tyrosine phosphorylation of cellular proteins. Therefore, our findings indicate that in 697/BCL-2 cells, high levels of p26BCL-2 significantly delay taxol-induced endonucleolytic internucleosomal DNA fragmentation and apoptosis, but do not affect taxol-induced microtubule bundling or cell cycle growth arrest. The delayed onset of taxol-induced DNA fragmentation and apoptosis in 697/BCL-2 cells without down-regulation of p26BCL-2 levels suggests that an alternative mechanism of taxol-mediated apoptosis might be triggered which is unimpeded by high p26BCL-2 levels, or taxol-induced prolongation of mitotic arrest may lead to the inactivation or inhibition of that mechanism by which p26BCL-2 is able to block apoptosis.
Leukemia 1994 Nov
PMID:High levels of p26BCL-2 oncoprotein retard taxol-induced apoptosis in human pre-B leukemia cells. 752 93

Murine monoclonal antibody (mAb) 7C11 binds to the same cell surface epitope as anti-APO-1 and anti-Fas and reacts specifically with cells transfected with a cDNA encoding the human Fas antigen. Furthermore, incubation with 7C11 causes death of hematopoietic cell lines that express APO-1/Fas but not APO-1/Fas-negative cell lines. 7C11 therefore recognizes the human APO-1/Fas (CD95) antigen, a 40 to 50 kDa cell surface glycoprotein that can trigger apoptosis or programmed cell death. Expression of APO-1/Fas antigen by normal and neoplastic hematopoietic cells was determined by flow cytometry using 7C11. APO-1/Fas is expressed by approximately 30 to 40% of resting peripheral blood T cells, B cells, and monocytes and by approximately 5% of resting NK cells and thymocytes. It was not detected on granulocytes, erythrocytes, or platelets. Approximately 80 to 90% of activated T cells, B cells, and thymocytes express APO-1/Fas, as do the majority of activated NK cells. Perturbation of APO-1/Fas by 7C11 does not affect the viability of resting lymphocytes or monocytes. In contrast, activated T cells and NK cells undergo apoptosis within 3 hours of exposure to 7C11. Other mAb that stimulate T cells or NK cells do not cause rapid induction of programmed cell death. APO-1/Fas antigen is expressed by many cell lines of lymphoid and myeloid lineage. However, this antigen was detected on neoplastic cells from only one of 69 patients with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, or multiple myeloma. Only 3 out of 25 tumor samples from patients with non-Hodgkin's lymphoma were found to express APO-1/Fas. All three of these lymphomas harbored the bcl-2-Ig fusion gene associated with the chromosomal translocation t (14;18). Conversely, only 27% of lymphomas that possessed the bcl-2-Ig gene were found to express the APO-1/Fas antigen. Like normal activated lymphocytes, leukemia and lymphoma cells that expressed APO-1/Fas antigen were found to undergo apoptosis in vitro after incubation with 7C11. The APO-1/Fas antigen appears to regulate the growth of normal hematopoietic cells, and the marked upregulation of this antigen on activated normal lymphocytes contrasts sharply with the absence of APO-1/Fas on neoplastic cells of hematopoietic lineage. Defects in the apoptotic signal delivered through this antigen might contribute to the pathogenesis of hematopoietic neoplasms. Thus, the gene encoding APO-1/Fas can be considered a novel type of tumor suppressor gene, just as bcl-2 can be considered a cellular proto-oncogene.
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PMID:Functional consequences of APO-1/Fas (CD95) antigen expression by normal and neoplastic hematopoietic cells. 753 60

The expression of bcl-2 protein that is involved in preventing apoptosis in hemopoietic and other cells was evaluated by quantitative flow cytometry in various subpopulations in the normal fetal bone marrow (FBM) and in different types of acute myelogenous leukemias (AML). In the FBM the highest bcl-2 levels (mean antibody binding capacity 51 x 10(3) molecules/cell) were found in CD34+ intermediate sized blasts and myeloblasts, while a CD34+ subset of CD10+ lymphoblasts had low bcl-2 content (8-10 x 10(3) molecules/cell) and the CD34-, CD10+ lymphoblasts were, as expected from previous studies, bcl-2- (< 5 x 10(3) molecules/cell). Variable levels of bcl-2 (5.1-222 x 10(3)) were found in 43 tested cases of AML. The bcl-2 levels decrease with granulocytic and monocytic differentiation and, accordingly, cases of AML with M1 and M2 features showed significantly higher mean bcl-2 levels than the leukemias with promyelocytic (M3) or myelo-monocytic (M4/M5) features. Nevertheless, in seven cases of AML the bcl-2 levels were higher than seen in the normal FBM cells and none of these patients remain in remission after 2 years. Furthermore, in several AML cases intraclonal heterogeneity was observed. The undifferentiated smaller blasts with Class-IIdim display had higher bcl-2 content than the more differentiated larger blasts with more granular side scatter and Class-bright expression. In the same subsets of AML blasts the proliferative S-G2-M fractions showed a reciprocal correlation to bcl-2 content. Thus the higher bcl-2 levels may give a survival advantage and confer some degree of drug resistance to the least differentiated blast populations. The multi-parameter analysis described in this paper, including a combined bcl-2 and cytokinetic analysis of phenotypically defined subgroups of AML blasts, may detect early population shifts during relapse and also guide combination drug therapy.
Leukemia 1995 Jul
PMID:Bcl-2 protein expression in normal human bone marrow precursors and in acute myelogenous leukemia. 754 74

The expression and function of the FAS antigen was analyzed in 21 patients with B chronic lymphocytic leukemia (CLL) and four with hairy cell leukemia (HCL) using a specific IgM monoclonal antibody and FACS analysis. The FAS antigen was expressed in a minority (5-41%, mean 15.6%) of the CLL cells in 10 of 21 CLL patients and this expression was not modified during spontaneous or hydrocortisone-induced apoptosis of CLL cells. In contrast, culture with gamma-interferon (gamma-IFN) upregulated the expression of FAS in all CLL patients, with 65-100% (mean 84.8%) of the cells being positive after 2 days in vitro culture. Culture with alpha-IFN induced FAS expression in 15 of 19 CLL patients tested, with 15-74% (mean 34%) of the cells being FAS+ after 2 days culture. IL-4 and IL-10, lymphokines that inhibit and promote CLL apoptosis respectively, did not modify the expression of FAS. These results from FACS analysis were consistent with FAS mRNA analysis of fresh and cultured CLL cells, using a semi-quantitative reverse transcriptase (RT)-PCR technique. Although IL-4 and IFNs prevent apoptotic cell death of CLL cells in vitro, the present results show that IFNs induce the expression of the apoptosis-inducing protein FAS. However, FAS+ CLL cells were not killed in the presence of anti-FAS monoclonal antibody (while the FAS+ Jurkat and four lymphoblastoid cell lines were killed). This resistance is not due to a mutated FAS protein, since only wild-type FAS cDNA was demonstrated in the leukemic cells of three CLL patients. In four HCL patients 34-53% (mean 44.5%) of the leukemic cells were FAS+ and they were also resistant to the anti-FAS mediated cytotoxicity. The combination of high bcl-2 protein levels and resistance to anti-FAS mediated cytotoxicity may contribute to the extended in vivo survival of CLL and HCL cells.
Leukemia 1995 Jul
PMID:Expression and function of the FAS antigen in B chronic lymphocytic leukemia and hairy cell leukemia. 754 75

This review attempts to provide current information on the role played by the p53 gene in normal and leukemic hematopoiesis with particular emphasis on chronic myeloid leukemia. On the basis of the currently available data we can argue that p53 acts as a negative regulator of proliferation of myeloid mature cells and CD34+ progenitors, and its action is mediated through changes in cell cycle kinetics, mainly before the S phase. The p53-dependent pathway is also regulated by several proteins, including p16, p21, p27 (cyclin-dependent kinase [CDK] inhibitors), and a few oncogenes (bcl-2, bax, MDM-2). Although there is some information about the changes in the p53 gene seen in various types of leukemia, the functions and biological importance of these changes in the pathogenesis of leukemia are still largely elusive. During the past several years, accumulated evidence suggests that changes in the p53 gene are commonly associated with blast crisis of chronic myeloid leukemia (CML) but rarely with chronic phase, and they are represented by rearrangements, deletions and point mutations. As for most of the tumors, the majority of point mutations occur between exons 4 and 8 (hot regions). In patients with CML in blastic crisis the most frequent mechanism of p53 inactivation is complete deletion of one allele in association with a point mutation in the remaining allele.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of p53 in leukemogenesis of chronic myeloid leukemia. 754 4

All-trans retinoic acid (ATRA) increases the sensitivity of AML blast cells to cytosine arabinoside (Ara-C) or daunorubicin (DNR) when ATRA is given after drug. We have proposed that down-regulation of bcl-2 is part of the mechanism by which ATRA regulates drug sensitivity. To test this hypothesis cDNA encoding bcl-2 was transfected into cells of the continuous lines OCI/AML-2 and OCI/AML-5. Four transfectant lines were isolated; three contained transfected bcl-2 in the sense orientation (AML5-BCL2sa, AML5-BCL2sb and 2-bcl2) and one with anti-sense bcl-2(AML5-bcl2as). The presence of the transfected gene was demonstrated by Northern blot; translation of the sense transfected genes into protein was demonstrated by Western blotting. Lines with sense-oriented transfected bcl-2 were significantly less sensitive to Ara-C or H2O2 than the parental lines; the cells with anti-sense transfected genes were more sensitive than their parent but the difference did not reach statistical significance. The effect of ATRA on bcl-2 expression was compared in sense-transfected cells and their parents; by Northern blotting it was shown that the endogenous but not the transfected genes were down-regulated after ATRA exposure. The capacity of cells with transfected genes to respond to ATRA was tested by obtaining Ara-C survival curves for ATRA-treated cells. Compared to controls not exposed to ATRA, the transfected cells showed little or statistically insignificant changes in Ara-C sensitivity after ATRA treatment. We conclude that data from the transfectants provides evidence that expression of bcl-2 is a determinant of sensitivity to Ara-C and H2O2; and that the effect of ATRA on sensitivity requires the presence of bcl-2 genes in association with regulatory elements.
Leukemia 1995 Oct
PMID:Direct evidence for the participation of bcl-2 in the regulation by retinoic acid of the Ara-C sensitivity of leukemic stem cells. 756 7

Murine acquired immunodeficiency syndrome (MAIDS) is caused by a defective murine leukemia virus. The disease is characterized by abnormal lymphoproliferation, impaired T and B cell function and aberrant regulation of cytokines. Both T and B lymphocytes show activated phenotypes, but undergo apoptotic death with characteristic DNA fragmentation. These results indicate the presence of a continuous activation death pathway of the lymphocytes in MAIDS. Overexpression of the bcl-2 transgene in lymphocytes showed no effect on the apoptotic cell death or on the development of the disease. In contrast, mice carrying mutations in either Fas or Fas ligand exhibited accelerated progression of the disease upon infection with MAIDS virus. These results suggest the involvement of Fas-Fas ligand system in the pathogenesis of MAIDS.
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PMID:Apoptotic death of lymphocytes in murine acquired immunodeficiency syndrome: involvement of Fas-Fas ligand interaction. 758 5

The oncoprotein bcl-2 can be expressed in malignant plasma cells and might play a role in the prevention of corticosteroid-mediated apoptosis, thereby prolonging survival of the myeloma cells. We retrospectively investigated whether bcl-2 expression in bone marrow plasma cells measured by two-color fluorescence for immunoglobulin light chains would be related to survival duration in patients suffering from multiple myeloma. In all patients the large majority of plasma cells expressed bcl-2 (median 91%, range 74-100%). Contrary to our expectations, a tendency was observed toward higher percentages bcl-2+ plasma cells in patients with a long survival (more than 5 years, n = 9) vs patients who died from refractory myeloma within a year of diagnosis (n = 7). This tendency was found even when analysis was extended to include four patients in the short diagnosis group (n = 11) who had received chemotherapy prior to bone marrow examination.
Leukemia 1995 Jul
PMID:Bcl-2 protein expression is not related to short survival in multiple myeloma. 763 Feb 4

The biological activity of a novel synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN) was investigated in human breast carcinoma (HBC) cells. Although capable of selective binding to the RAR gamma nuclear receptor, AHPN inhibited the growth of a number of HBC cell lines via RAR- or RXR-independent pathways. AHPN also inhibited the growth of the human leukemia cell line HL-60R which does not possess functional RARs. RA significantly inhibited AP-1 mediated gene activation in MCF-7 cells while AHPN displayed no such anti-AP-1 activity. Retinoids normally are cytostatic in their inhibition of breast carcinoma growth and permit cell proliferation upon their removal, wher as AHPN induced G0/G1 arrest within 6h followed by apoptosis. In MCF-7 cells that harbor wild type p53, AHPN-induced G0/G1 arrest and apoptosis was accompanied by p53-independent regulation of WAF1/CIP1 as well as bax mRNA levels while bcl-2 mRNA levels were decreased. In MDA-MB-231 cells which possess a mutant p53, AHPN-mediated G0/G1 arrest and apoptosis was also associated with a concomitant up regulation of WAF1/CIP1 mRNA while these cells did not express bax or bcl-2 messages. Thus AHPN represents a novel retinoid that induces G0/G1 arrest and apoptosis via a unique pathway which appears to involve activation of known downstream effectors of p53 in a p53-independent manner.
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PMID:p53 independent G0/G1 arrest and apoptosis induced by a novel retinoid in human breast cancer cells. 763 Jun 33


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