Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A human genomic fragment comprising the cellular retinoic acid binding protein (CRABP) gene was isolated. By using a panel of somatic cell hybrids, this gene could be assigned to human chromosome 15. Subsequently, a possible involvement of the CRABP gene in translocation (15;17) (q22;q11) positive acute promyelocytic leukemia (APL) was investigated. Although transposition of the CRABP gene could be demonstrated, we did not observe any gross CRABP rearrangement in a series of primary APL patients, nor in the acute myeloblastic leukemia cell line HL-60. Thus, the observed lack of CRABP expression in these leukemic cells may not be caused by disruption of its gene. CRABP maps to the region 15q22-qter.
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PMID:Localization of the cellular retinoic acid binding protein (CRABP) gene relative to the acute promyelocytic leukemia-associated breakpoint on human chromosome 15. 164 46

Expression of a mRNA cross-hybridized to human cytomegalovirus immediate-early gene promoter-enhancer was detected in the human promyelocytic leukemia cell line HL-60. The 0.6 kilobase of NruI/SacI DNA fragment of eukaryotic expression vector pCDM8 representing human cytomegalovirus immediate-early gene promoter-enhancer was used as the probe to hybridize with polyadenylated RNA by the Northern blot analysis. A 3.7-kilobase strand of polyadenylated RNA was visualized in the cytoplasmic fraction of HL-60 promyelocytes. In contrast, other human hematopoietic cell lines, hepatoma cells, and normal human fibroblasts did not show such a transcript by cross-hybridization. This transcript was called CMVE RNA. The expression of CMVE mRNA was also detectable in the fresh blast cells from patients with acute myeloid leukemia, and particularly from a patient with acute myeloid leukemia of the M3 type. Taken together, these findings suggest that the CMVE RNA-encoded gene plays an important role in the pathogenesis of acute promyelocytic leukemia.
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PMID:A single 3.7-kilobase messenger RNA hybridizes to immediate-early promoter enhancer of human cytomegalovirus in HL-60 and acute myeloid leukemia cells. 165 11

We have recently demonstrated that all-trans retinoic acid (RA), the active metabolite of vitamin A, is an efficient alternative to chemotherapy in the treatment of acute promyelocytic leukemia (AML3). We have further shown that, in these AML3 cells, the gene of the retinoic acid receptor-alpha (RAR alpha) is translocated from chromosome 17 to chromosome 15, and fused to a new gene, PLM. This results in the expression of both normal and chimeric RAR alpha transcripts in AML3 cells. The PLM-RAR alpha protein may account for the impairment of differentiation and thus leukemogenesis, but not for the paradoxical efficacy of RA in these cells. In an attempt to elucidate RA's differentiative effect in AML3 patients, the present work examined the in vitro and in vivo modulation of the normal RAR alpha transcripts by all-trans RA in seven cases of AML3. In all samples, Northern blot analysis revealed a low expression of the two normal RAR alpha transcripts compared with other human myeloid leukemic cells. No modulation was observed after 4-8 d of in vivo therapy with all-trans RA 45 mg/m2 per d. In vitro incubation with all-trans RA, however, increased the level of expression of the normal RAR alpha transcripts in AML3 cells but not in other AML leukemic subtypes. This modulation of the two normal RAR alpha transcripts appeared to be an early and primary event of RA's differentiating effect. We therefore suggest that up-regulation of the normal RAR alpha gene expression by pharmacological concentrations of all-trans RA may restore the normal differentiation pathway in these cells.
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PMID:All-trans retinoic acid modulates the retinoic acid receptor-alpha in promyelocytic cells. 166 1

The in vitro growth response of bone marrow and blood cells to granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) was studied in 18 acute myeloid leukemia (AML) patients using semisolid and suspension cultures. In 80% of the cases growth of leukemic progenitor cells was stimulated by GM-CSF and/or G-CSF, as judged by colony or cluster formation. In acute promyelocytic leukemia [t(15;17)], G-CSF stimulated and maintained the leukemic progenitors only transiently but fully stimulated the residual normal granulocyte/macrophage colony-forming units (CFU-GM). In some cases of M2 and M4 leukemia, G-CSF enhanced markedly the production of mature but cytochemically abnormal neutrophils. In some cases of M1 leukemia, neither CSF stimulated leukemic progenitors but instead stimulated only residual normal granulopoiesis. Spontaneous colony formation was observed in 20% of cases and was correlated with high-grade leukemic growth in vivo and a poor response to chemotherapy. The differing effects of the CSFs upon leukemic cells and residual normal granulopoiesis may have some implications for the clinical use of GM-CSF and G-CSF to overcome infectious complications.
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PMID:In vitro growth response to G-CSF and GM-CSF by bone marrow cells of patients with acute myeloid leukemia. 169 Aug 27

Human granulocyte colony-stimulating factor (G-CSF) receptors on human acute leukemia cells were investigated using human G-CSF iodolabeled by the lactoperoxidase method. Among various human leukemic cell lines, only cells of myelogenous lineage including HL-60, THP-1 and U937 had one type of high-affinity receptor for G-CSF, as shown by Scatchard analysis. Fresh leukemia cells from 19 patients with acute myelogenous leukemia (AML) were then studied. Specific receptors for G-CSF were demonstrated on blast cells in all 19 cases, the mean number of G-CSF receptors per AML cell ranging from 95 to 1436. G-CSF receptors on AML cells appeared to be a single affinity type, although some variations were observed. The mean number of G-CSF receptors on leukemic cells from patients with either FAB M3 or FAB M2 was greater than that of cells from patients with M1 (p less than 0.01, p less than 0.10, respectively). Moreover, the mean number of receptors for G-CSF on CD13- and CD34-positive AML cells was higher than that on CD13-negative and CD34-positive AML cells (p less than 0.01), and the mean number of G-CSF receptors on CD7-positive AML cells was lower than that for CD7-negative AML cells (p less than 0.10). Since the FAB classification and surface phenotypes reflect maturation stages, our findings indicate that the distribution of G-CSF receptors, even on AML cells, may be related to the maturation process.
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PMID:Human granulocyte colony-stimulating factor receptors in acute myelogenous leukemia. 170 27

We studied the expression of cell surface antigens associated with myeloid and lymphoid leukemias on bone marrow-derived blast cells from 339 patients with newly diagnosed de novo acute myeloid leukemia (AML) enrolled on Cancer and Leukemia Group B (CALGB) chemotherapy protocols. Surprisingly, of 211 cases studied for the expression of CD2 (T-cell marker, sheep erythrocyte binding receptor for T lymphocytes) 45 were positive (21%). In addition, of 298 patients studied for CD19 (B-lymphocyte marker), 41 were positive (14%). Overall, of 170 patients studied for both CD2 and CD19, 56 (33%) were positive. Interestingly, central review of the French-American-British (FAB) morphology of the CD2- and CD19-positive cases showed that FAB M3 was twice as frequent, and M4E eight times as frequent compared with the CD2- and CD19-negative cases. Of 22 lymphocyte antigen-positive cases in which cells were available for studies of Ig or T-cell antigen receptor (TCR) gene rearrangement, 20 were germline, one had a rearranged Ig heavy chain gene, and one had rearranged TCR beta and Ig heavy chain genes. The presence of messenger RNA for CD2 was demonstrated in four CD2 surface antigen-positive cases, thus validating the cell surface data. Lymphocyte antigen-positive cases had karyotypes commonly seen in AML; 71% of cases with an abnormal clone had t(8;21)(q22;q22), inversion 16(p13q22), t(15;17)(q22;q12), or t(9;11)(p22;q23). The patients with lymphocyte markers had a significantly higher incidence of these karyotypic abnormalities compared with patients with lymphocyte antigen-negative AML (34% v 15%, P less than .02). When the outcome to therapy of the lymphocyte antigen-positive cases was compared with that for the CD2, CD19-negative cases, we found that the CD2, CD19-positive cases actually had higher complete remission rates (75% v 59%, P = .04), and significantly longer time to failure (P = .02; 32.4% +/- 6.0% v 18.0% +/- 4.1% at 2 years) and overall survival (P = .02; 43.5% +/- 6.3% v 26.0% +/- 4.5% at 2 years). CD2 antigen-positive cases also had a significantly superior survival (P = .02; 43.8% +/- 7.9% v 29.8% +/- 3.8% at 2 years). There were no significant differences (P less than or equal to .05) between the two groups in age, leukocyte count at diagnosis, incidence of extramedullary disease, or FAB classification.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Prognostic value of lymphocyte surface markers in acute myeloid leukemia. 137 22

Acute leukemia has become a curable disease. In 3 studies for adult AML (BHAC-DMP, BHAC-DMP (II) and M-85) at Nagoya University Hospitals from 1979 to 1987, intensive induction resulted in higher cure rate, and the reduction of the blasts in bone marrow at 2 weeks after the initiation of therapy to less than 20% was the most important prognostic factor to predict the long CR. However, it seemed impractical to give very intensive chemotherapy during the induction because of high frequency of complications due to prolonged myelosuppression. Thus, consolidation should be as intensive as possible. In M-85 protocol, the predicted 5-years survival and disease-free survival (DFS) of CR cases are 70 and 53% respectively. The result of JALSG-AML 87 study seems to confirm the above result. As for the indication of bone marrow transplantation (BMT) at the first CR for adult AML, only a prospective randomized study will answer this important question. In case that DFS of chemotherapy will exceed 40 to 45%, it seems be wise to give chemotherapy first, and then BMT when the leukemia relapse. Differentiation induction therapy seems to be indicated in acute promyelocytic leukemia, although a confirmative study is awaited.
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PMID:[Recent progress in the treatment of acute leukemia]. 171 2

Phenotypes of cells from 12 patients with acute myelogenous leukemia (AML) were analysed by means of a fluorescence-activated cell sorter utilizing a panel of monoclonal antibodies (MAbs). A majority of the cells from peripheral blood coexpressed the antigens against MAbs CD11, CD13, and CD33 but did not express the antigens against CD1, CD3, CD4, CD5, CD8, CD19, CD20, CD21, CD41 and 42, and glycophorin A. Three out of the 12 cases expressed CD7 antigen. However, one of them showed no reaction with Tp40 MAb, whereas the others showed reaction with Leu9 and T55. The discrepancy of reactivities between Leu9 and Tp40 MAbs prompted us to study the promyelocytic leukemia cell line HL-60, which showed similar reactions against Leu9 and Tp40 MAbs. Leu9, OKT16, and T55 MAbs reacted strongly with HL60 cells, whereas Tp40 MAb, which reacted strongly with T-cell leukemia cell line Jurkat, showed no reaction. The reactivity of Leu9, OKT16, and T55 MAbs with HL-60 cells was completely inhibited after preincubation with aggregated human immunoglobulin G (AHIG), which clearly shows the existence of nonspecific binding between these 3 MAbs and HL-60 cells via Fc gamma R. On the basis of our experiments, we conclude that HL-60 cells bind nonspecifically with Leu9, OKT16, and T55 MAbs via FcRI, and this is suggestive that de novo AML cells probably behave in the same fashion. Hence, we recommend that the utilization of murine IgG2a and IgG3 MAbs should be avoided especially in cell surface analysis of myeloid leukemic cells.
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PMID:CD7 false-positive acute myelogenous leukemia and promyelocytic leukemia cell line HL-60: characterization of CD7 epitopes by four monoclonal antibodies. 171 52

Chronic exposure of humans to benzene has been shown to have a cytotoxic effect on hematopoietic progenitor cells in intermediate stages of differentiation, which can lead to aplastic anemia and acute myelogenous leukemia. We studied the effect of hydroquinone (HQ), a toxic metabolite of benzene found in the bone marrow, on the human promyelocytic leukemia cell line (HL-60), which can be induced to differentiate to both monocyte and myeloid cells, and thus has been used as a surrogate for a granulocyte/macrophage progenitor cell. Exposure of HL-60 cells to noncytotoxic concentrations of HQ for 3 hours before induction with phorbol myristate acetate (TPA) caused a dose-dependent inhibition of the acquisition of characteristics of monocytic differentiation, such as adherence, nonspecific esterase (NSE) activity, and phagocytosis, but had no effect on cell proliferation. HQ appeared to be affecting maturation beyond the monoblast/promonocyte stages. HQ also prevented differentiation induced by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]; however, the block occurred after the acquisition of adherence. HQ at concentrations that inhibited monocytic differentiation had no effect on differentiation to granulocytes, suggesting that the block in the differentiation of these bipotential cells is a step unique to the monocytic pathway. HQ was unable to prevent differentiation induced by the macrophage-derived cytokine, interleukin (IL)-1, a differentiation factor for cells of the monocytic lineage.
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PMID:Induced differentiation of HL-60 promyelocytic leukemia cells to monocyte/macrophages is inhibited by hydroquinone, a hematotoxic metabolite of benzene. 173 8

We describe herein a patient with acute promyelocytic leukemia (APL)-(ANLL-M3) whose bone marrow cells in the second relapse showed t(1;3)(p36;q21) together with t(15;17) (q22;q11-q12). Although a total of 21 patients with t(1;3) have been reported so far, among which three cases with de novo acute nonlymphocytic leukemia were included, our patient is the first case with APL. The hematologic findings in our case confirmed the previous observations that this anomaly is associated with relatively high platelet count and the multi-myeloid lineage involvement of leukemic cells. Our patient responded well to chemotherapy and achieved first and second remission with 42 months of total survival, contrary to our expectation that patients with this anomaly have a poor prognosis.
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PMID:Second relapse of acute promyelocytic leukemia (ANLL-M3) with t(15;17) and t(1;3)(p36;q21). 175 85


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