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

Previous studies suggest that malignant cells from some patients with myeloid leukemias produce colony-stimulating factors (CSFs) that can function as autocrine growth factors in vitro. We have examined the roles of interleukin-6 (IL-6) and granulocyte-macrophage CSF (GM-CSF) in the proliferation of myeloid leukemia cells. IL-6 activity was assessed in conditioned medium (CM) from myeloid leukemia cell cultures or cell lysates using IL-6-dependent KD83 and 7TD1 murine cell lines. Media conditioned by cells from patients with chronic myelomonocytic leukemia (CMMoL), but not by normal monocytes, chronic myelogenous leukemia (CML), or acute myelogenous leukemia (AML) cells, contained substantial levels (50 to 1,000 U/10(6) cells) of IL-6. The IL-6 content of CM correlated directly with donor peripheral blood WBC count. CM from two of five CMMoL samples also contained greater than 350 pg/mL GM-CSF. Moreover, CMMoL cells spontaneously formed colonies in semisolid medium. CMMoL colony formation could be partially inhibited by antibodies to IL-6 or GM-CSF, whereas combination of these antibodies gave additive, and nearly complete (greater than 93%), inhibition of spontaneous colony formation. Cell lysates from uncultured CMMoL cells from one patient contained abundant GM-CSF protein but no detectable IL-6. These data suggest that IL-6 and GM-CSF act in vitro as autocrine growth factors for CMMoL cells, and that CMMoL cells in vivo may represent a GM-CSF-dependent autocrine growth system.
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PMID:Interleukin-6 and granulocyte-macrophage colony-stimulating factor are candidate growth factors for chronic myelomonocytic leukemia cells. 267 12

Low-density blood cells from patients with refractory anemia with excess of blasts (RAEB) and RAEB in transformation (RAEB-T) release a high molecular weight inhibitory substance that reduces the entry of normal progenitor cells of granulocytes and macrophages (CFU-GM) into the S-phase. Out of 20 patients with refractory anemia (RA and RAS) only 3 were positive. One patient with CMML was negative. Serial examination of 3 patients (two RA and one CMML) revealed that the production of the inhibitory activity preceded the development of the disease into RAEB, RAEB-T, or AML. With one exception, the inhibitory activity in positive cases was neutralized by antiserum against human placental ferritin.
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PMID:Inhibitor of normal granulopoiesis produced by cells of MDS patients. 270 26

We tried to treat 13 patients with myelodysplastic syndromes (MDS), leukemias and myeloproliferative disorders, with alfacalcidol for their hematological improvement. Eight of them had MDS, 2 acute leukemia (M3, M4), 1 chronic myelogenous leukemia and 2 primary myelofibrosis. All patients were untreated except for 3 patients (PASA, RAEB, AML-M4) who had been treated with mepitiostane, prednisolone and BH.AC-AMP regimen, respectively, prior to alfacalcidol therapy. All patients received alfacalcidol orally for at least one month. The dosage of alfacalcidol ranged from 0.25 to 10 micrograms/day, and the medicine was administrated intermittently when the dosage exceeded 6 micrograms/day to prevent hypercalcemia. The therapeutic effectiveness of alfacalcidol was evaluated according to a criteria by Koeffler (Cancer Treat Rep 69: 1399, 1985) with minor modifications. Three patients (PASA, RAEB, CMML) showed partial response, 3 (RAEB, RAEB in T, AML-M4) minor response and rest of the patients did not respond. The hematological improvement of 6 responders was transient (from 1 to 2 months), however, one patient (PASA) is still responding to alfacalcidol therapy (0.25 microgram/day) for over 12 months. The dysplastic features of hemopoietic cells in the bone marrow showed no noticeable change during the hematological improvement in these responders, suggesting the improvement was obtained as a result of alteration in the proliferation or differentiation of neoplastic clone. None of 13 patients developed hypercalcemia. One patient (AML-M4) became excitable on high dose alfacalcidol (10 micrograms/day). In conclusion, alfacalcidol therapy is effective in some patients with MDS or leukemias and appears worthy especially in the clinical state in which chemotherapy is not indicated.
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PMID:[Therapeutic effectiveness of vitamin D3 in patients with myelodysplastic syndromes, leukemias and myeloproliferative disorders]. 271 94

We examined the capacities of sera from patients with myeloid leukemia to induce differentiation in mouse myeloid leukemic M1 cells. Higher differentiation-inducing activity (D-activity) was detected in sera of patients with chronic myelomonocytic leukemia or chronic myeloid leukemia (CML) than in sera of patients with acute myeloid leukemia and normal volunteers. The D-activity in the sera was lost on heating the sera at 56 degrees for 30 min. The major peak of D-activity on Sephadex G-200 gel filtration had an apparent molecular weight of 160,000. The origin of the D-activity in sera of patients with CML was studied by culturing fractions of peripheral blood cells of patients with D-activity for 3 days and then measuring the ability of the conditioned medium (CM) to induce differentiation of M1 cells. The cells in the myeloblast and promyelocyte fraction differentiated spontaneously into macrophage-like cells during culture for 3 days and the cells in the late granulopoietic cell fraction differentiated into neutrophil-like cells. Higher D-activity was present in CM of cells in the myeloblast and promyelocyte fraction than in CMs of late granulopoietic cell fractions. These results suggest that human leukemic cells produce D-activity for M1 cells during their differentiation into macrophage-like cells.
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PMID:Induction of differentiation of mouse myeloid leukemia M1 cells by serum of patients with chronic myeloid leukemia. 314 2

Members of the RAS gene family have been implicated in many neoplasms with activating mutations around amino acid positions 12 and 61. We have assessed the mutational activation of H, K, and NRAS in myelodysplasia (MDS) by polymerase chain reaction and hybridization with synthetic oligonucleotide probes. Using this method, point mutations in codons 12/13 and 61 of these RAS genes were detected in 20 of 50 patients including two with refractory anemia with ringed sideroblasts (RARS). Ten normal individuals had no detectable RAS mutations. In 11 instances, DNA from patients with detectable RAS mutations were shown to register in either NIH3T3 focus-forming or nude mouse tumorigenicity assays. In addition, one patient (RARS) was shown to have an activated NRAS gene detected by a tumorigenicity assay and Southern blot analyses. Two MDS patients had mutations detected in two different RAS genes. DNA from one of these patients was observed to give rise to transformants with activated N and HRAS. Two patients with detectable NRAS mutations in the MDS stage progressed to AML and DNA from the AML stage registered positively in a transformation assay with NRAS activation. These results show that RAS mutations can occur at early, as well as late, stages of leukemic progression. The incidence of RAS mutations appears to be significantly higher in CMML than in the other subgroups (p = 0.02).
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PMID:RAS mutations in myelodysplasia detected by amplification, oligonucleotide hybridization, and transformation. 316 76

Two cases of chronic myelomonocytic leukemia (CMMoL) with trisomy 11 as the sole chromosome abnormality are reported. A simple trisomy 11 also has been reported in 11 patients with myeloproliferative disorders, including CMMoL and acute nonlymphocytic leukemia (ANLL) in the literature. From data on these 13 patients, leukemia with trisomy 11 may be characterized by a nonlymphoid origin and myelomonocytic features. Patients with this abnormality were mostly elderly, and often had a preleukemic phase and a short survival. We propose that trisomy 11 and nonlymphocytic leukemia with myelomonocytic features may be a new association in human neoplasia.
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PMID:Trisomy 11 in chronic myelomonocytic leukemia: report of two cases and review of the literature. 327 88

Somatic mutation of the N-ras oncogene occurs frequently in de novo acute myeloid leukemia (AML). By virtue of their relation to AML, myelodysplastic syndromes (MDS) provide an in vivo model of human leukemogenesis. By using a strategy for analysis of gene mutation based on in vitro amplification of target sequences by the polymerase chain reaction (PCR) and selective oligonucleotide hybridization we analyzed the mutational status of codons 12, 13, and 61 of Ha-ras, K-ras, and N-ras in peripheral blood (PB) and/or bone marrow (BM) in 34 cases of primary MDS. Mutations at codon 12 of Ki-ras or N-ras were detected in three cases (9%): one of six cases of refractory anemia with excess blasts (RAEB) and two of nine cases of chronic myelomonocytic leukemia (CMML). The nucleotide substitution differed in each. In all cases the mutant allele was detectable in PB cells. A sustained hematologic remission was achieved after low-dose cytarabine therapy in the case of RAEB. Neither case of CMML exhibited signs of disease progression during follow-up at 7 and 12 months. In contrast, four of 31 patients without the ras mutation underwent transformation to AML within 12 months of genetic analysis. We conclude that ras mutations in MDS are heterogeneous and may develop at an early stage during the evolution of MDS. Their detection in PB cells illustrates the potential utility of ras mutation as a clonal marker in myeloid malignancy.
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PMID:Mutation of Ki-ras and N-ras oncogenes in myelodysplastic syndromes. 328 9

Two cases of childhood myelodysplastic syndrome with chromosome abnormalities involving band 11p15 are described. The first case, with inv(11)(p15q23), had a complex clinical course; the initial diagnosis was aplastic anemia, then refractory anemia with excess of blasts in transformation (RAEB-t), and finally, before death, chronic myelomonocytic leukemia with hematologic features similar to those of chronic myelogenous leukemia (CML). The second case, with t(4;11)(p13;p15), progressed from RAEB to acute myelogenous leukemia (M2). In the literature, we found 12 patients with nonlymphocytic leukemia and chromosome abnormalities involving band 11p15, including seven cases with t(7;11)(p13-p15;p15); four cases (including the present case 1) showed CML-like hematologic features. It is suggested that translocations involving 11p15 are a nonrandom chromosome abnormality in nonlymphocytic leukemia.
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PMID:Childhood myelodysplastic syndromes with 11p15 translocation. 329 71

Between 1980 and 1986, we diagnosed refractory anaemia (RA), according to the FAB classification, in 69 patients, who constituted 22% of the 312 cases of myelodysplastic syndromes (MDS) seen over that period. The haematological features were variable, with pancytopenia in 14 cases (20%), bicytopenia in 24 (36%) and mono-cytopenia in the remaining patients, including 21 (30%) cases of anemia alone, 8 (12%) cases of refractory neutropenia and 2 (3%) cases of refractory thrombocytopenia. Myelodysplastic features were also quite variable, involving one, two or all three lineages. In patients with a single cytopenia or only one dysplastic lineage, FAB criteria appeared insufficient for adequate inclusion among RA and we suggest more precise diagnostic criteria, resulting from the utilization of cytogenetics, ferrokinetics, progenitor cultures and perhaps molecular biology, in such cases. Median survival was 42 months. 12 patients (17%) progressed to RAEB (of whom 7 finally developed ANLL) and 4 patients (6%) to CMML. In spite of the heterogeneity of haematological features, only two factors were associated with poor prognosis, namely age greater than 70 yr at diagnosis and haemoglobin less than 10 g/dl, whereas, to a lesser extent, neutropenia was associated with progression to RAEB.
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PMID:Refractory anaemia according to the FAB classification: a report on 69 cases. 336 22

Pluripotent (CFU-MIX), erythroid (BFU-E) and granulocyte/macrophage (CFU-GM) progenitor cells were examined in bone marrow (BM) from 23 patients with myelodysplastic syndromes (MDS). Patients were grouped according to the FAB classification: Refractory anemia (RA), n = 3; RA with ring sideroblasts (RARS), n = 3; RA with excess of blasts (RAEB), n = 8; RA with excess of blasts in transformation (RAEBt), n = 7; chronic myelomonocytic leukemia (CMML), n = 2. In FAB groups RA, RARS, RAEB and RAEBt CFU-GM concentrations were normal or decreased but both CMML-patients had increased CFU-GM values. Abnormal cluster growth was observed in 9 of 23 MDS-patients. BFU-E colony formation was subnormal in all cases. Mixed-colony assay values were at the lower limit of controls in one patient and decreased in the remaining 22 MDS-patients. A similar growth pattern of hemopoietic progenitor cells was observed in 19 patients with acute nonlymphocytic leukemia (ANLL), who were studied for comparison. These data suggest a quantitative or qualitative/functional defect of the pluripotent progenitor cell compartment as the major cause for the cytopenia in MDS-patients.
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PMID:Deficiency of pluripotent hemopoietic progenitor cells in myelodysplastic syndromes. 339 Jun 17


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