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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of human recombinant granulocyte and granulocyte-macrophage- (G- and GM-CSF), and of purified macrophage-stimulating factors (CSF-1), were tested on populations of leukemia cells isolated from 18 patients with different types of acute myeloid leukemia. Cell proliferation and differentiation were studied by culturing the cells in suspension for 7 days in the presence of CSF or medium alone. Spontaneous cell proliferation, as assessed by tritiated thymidine uptake, was observed in 9 of the 18 cases. GM-CSF induced proliferation in seven of the nine cases without spontaneous growth and increased spontaneous proliferation in nine cases. G-CSF added alone was also found to strongly stimulate leukemic blast cell proliferation, in which a translocation involving the long arm of chromosome 17 was observed. Low levels of CSF-1 stimulation were also observed in some cases. No clear morphological modification supporting evidence of terminal differentiation was observed, whereas modulation of some cell surface antigens was detected by flow cytometry. Thus, most leukemia cells still depend on growth factors for their proliferation, GM-CSF appearing the most effective. On the other hand these factors were not able to induce terminal differentiation.
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PMID:Growth response of human myeloid leukemia cells to colony-stimulating factors. 245 72

Cells from most cases of acute myeloblastic leukemia (AML) proliferate in vitro in response to one or more colony-stimulating factor (CSF). Previous studies have suggested that some AML cells can produce their own CSFs, but the frequency of this phenomenon is unclear. In this study, Northern blot hybridization was used to detect mRNA transcripts for granulocyte-monocyte CSF (GM-CSF), granulocyte-CSF (G-CSF), and macrophage-CSF (M-CSF) in 22 randomly selected cases of AML. Ten cases expressed one CSF transcript (generally M-CSF), one case expressed two CSF transcripts, and six cases expressed all three. The expression of CSF transcripts did not significantly correlate with the French-American-British classification, with the possible exception that four of the five cases expressing all three CSF mRNAs were FAB M1. Six cases had autonomous growth of clonogenic cells in agar, and all six cases expressed one or more type of CSF transcript. None of the five evaluated cases lacking all three CSF transcripts had autonomous growth. However, there were many cases in which CSF transcripts were present and no autonomous growth was observed. In response to exogenously added human recombinant CSFs, 11 of 18 cases proliferated in response to GM-CSF, 8 of 18 cases in response to G-CSF, and 0 of 10 cases in response to M-CSF. Response to a CSF was not significantly correlated with the presence or absence of CSF transcripts, particularly for M-CSF. These results show that CSF transcripts are frequently detected in AML, although with a substantial degree of heterogeneity. It is possible that CSF production contributes to unregulated growth in some cases of AML.
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PMID:In vitro expression of colony-stimulating factor genes by human acute myeloblastic leukemia cells. 245 74

The effects of human recombinant erythropoietin (rEpo) in the presence of other stimulators on the growth of clonogenic leukemic blast cells from ten Japanese patients with acute myeloblastic leukemia were studied with an in vitro leukemic blast colony assay in methylcellulose culture. With the addition of rEpo alone, no leukemic blast colony formation was stimulated in any of the cases examined. However, when rEpo and phytohemagglutinin lymphocyte-conditioned medium (PHA-LCM) were added to the culture simultaneously, in contrast to results with PHA-LCM alone, the number of leukemic blast colonies formed was significantly increased in two of the ten cases (P less than .01). These two cases were classified as M1 according to the French-American-British (FAB) classification. This enhancing effect of rEpo was observed with human recombinant granulocyte/macrophage colony-stimulating factor (rGM-CSF) or human recombinant interleukin-3 (rIL-3) but was not observed with human recombinant granulocyte CSF (rGCSF).
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PMID:Growth of clonogenic myeloblastic leukemic cells in the presence of human recombinant erythropoietin in addition to various human recombinant hematopoietic growth factors. 246 Jan 60

Monoclonal antibodies (MoAbs) have been prepared recently that recognize the three cell-surface receptors for the Fc portion of immunoglobulin (Ig), termed Fc gamma RI (MoAb 32.2), Fc gamma R II (MoAb IV-3), and Fc gamma R III (MoAb 3G8) that are expressed on selected subsets of non-T lymphocyte peripheral blood leukocytes. In the blood, Fc gamma R I is expressed exclusively on monocytes and macrophages, Fc gamma R II on granulocytes, mononuclear phagocytes, platelets, and B cells, and Fc gamma R III on granulocytes and natural killer (NK) cells. We have examined the expression of these molecules on normal bone marrow (BM) cells and on leukemia cells from the blood and/or BM in order to determine their normal ontogeny as well as their distribution on leukemic cells. BM was obtained from six normal volunteers and from 170 patients with newly diagnosed acute leukemia. Normal BM cells were found to express Fc gamma R I, II, and III with the following percentages: 40%, 58%, and 56%, respectively. Cell sorting revealed that both Fc gamma R I and Fc gamma R II were detectable on all subclasses of myeloid precursors as early as myeloblasts. Cell sorting experiments revealed that 66% of the granulocyte-monocyte colony-forming cells (CFU-GM) and 50% of erythroid burst-forming units (BFU-E) were Fc gamma R II positive with only 20% and 28%, respectively, of CFU-GM and BFU-E were Fc gamma R I positive. Acute myeloid leukemia (AML) cells expressed the three receptors with the following frequency (n = 146): Fc gamma R I, 58%; Fc gamma R II, 67%; and Fc gamma R III, 26% of patients. Despite the fact that Fc gamma R I is only expressed on monocytes among blood cells, AML cells without monocytoid differentiation (French-American-British [FAB]M1, M2, M3, M6) were sometimes positive for this receptor. However, Fc gamma R I was highly correlated with FAB M4 and M5 morphology (P less than .001). Fc gamma R II was also correlated with FAB M4 and M5 morphology (P = .003). Cells from 11 patients with acute lymphoblastic leukemia were negative for Fc gamma R I, but six cases were positive for Fc gamma R II and III (not the same patients). These studies demonstrate that Ig Fc gamma R are acquired during normal differentiation in the BM at or before the level of colony-forming units. In addition, we show that acute leukemia cells commonly express Fc gamma R.
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PMID:Expression of the three myeloid cell-associated immunoglobulin G Fc receptors defined by murine monoclonal antibodies on normal bone marrow and acute leukemia cells. 246 4

Autocrine growth mechanisms of leukemic blast progenitors in acute myeloblastic leukemia (AML) were investigated. Colony formation of leukemic blast progenitors was observed in 14 of 14 patients tested when purified blast cell fraction depleted of both T cells and monocytes was plated in methylcellulose without any colony-stimulating factor (CSF). However, there existed a minimal cell density required to initiate blast progenitor growth with marked patient-to-patient variation. To clarify the role of cell density on the spontaneous growth of blast progenitors, we tested whether leukemic cells produced and secreted some stimulatory humoral factor(s). Production of colony-stimulating activity (CSA) by blast cells was observed in 17 of 18 patients tested. Following further depletion of monocytes, the CSA levels decreased markedly in 14 patients, indicating that blast cells with monocytoid differentiation were responsible for CSA production. We also confirmed granulocyte colony-stimulating factor (G-CSF) and/or granulocyte macrophage-colony-stimulating factor (GM-CSF) production by leukemic blasts using specific immunologic assays. When leukemic cells were divided into nonadherent nonphagocytic cell fraction and adherent cell fraction, only nonadherent nonphagocytic cells showed clonogenecity and adherent blast cells lacked the colony-forming capacity. The results indicate that there are at least two blast cell subpopulations in AML: one is proliferating subpopulation with self-renewal capacity and the other is supporting subpopulation with functions such as CSF production. The quite intimate relationship between these two blast cell subpopulations in AML may play an important role on the growth of leukemic blast progenitors in vitro.
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PMID:Autocrine growth mechanisms of the progenitors of blast cells in acute myeloblastic leukemia. 247 99

Normal human myeloid cells require certain colony stimulating factors (CSFs) for growth and differentiation. These CSFs are normally produced exogenously by accessory cells. However, human acute myeloid leukemia cells have been found, in certain instances, to have constitutive, endogenous production of one or more of these CSFs. In order to address the molecular basis of this apparently anomalous production of CSFs, we studied granulocyte-, monocyte-, and granulocyte/monocyte colony stimulating factor gene expression, gene structure, transcription rate, message stability, and message inducibility in human acute myeloid leukemia samples. CSF gene expression by Northern analysis was variable from no transcripts detectable to transcripts present for all three CSFs. No CSF gene structure abnormalities were detected by Southern blot analysis. Nuclear run-on assays found ongoing and relatively uniform CSF gene transcription irrespective of the levels of CSF expression detected by Northern analysis. However, the stability of the CSF transcripts appeared to correlate with the level detected on Northern blots. Despite the apparent similarity in the regulation of these CSFs to that seen in mature monocytes, the inducibility of the expression of these CSFs was found to differ significantly from that seen in these mature myeloid cells. Taken together, these results suggest that the expression of CSF genes in human myeloid leukemias is primarily mediated through posttranscriptional mechanisms. These mechanisms are separate for each of the CSFs and apparently different from that found in normal blood monocytes.
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PMID:Colony-stimulating factor gene expression in human acute myeloblastic leukemia cells is posttranscriptionally regulated. 247 30

Respiratory burst develops in myeloid blast cells if they differentiate functionally along the monocytic or granulocytic lineage. Using the nitroblue tetrazolium (NBT) assay we studied the effects of recombinant human granulocyte/macrophage colony stimulating factor (rhuGM-CSF), rhuG-CSF and rhuM-CSF on development of respiratory burst activity in primary blast cells from patients with myeloid leukemia. Assessing suspension cultures containing cells from patients with acute myeloid leukemia (AML, n = 13) or myeloid-blast crisis (myBC) of chronic myeloid leukemia (CML, n = 5) it was found that the percentage of NBT positive cells was increased by at least 20% as compared to control cultures by rhuGM-CSF in 6/17 cases, by rhuG-CSF in 7/17 cases and by rhuM-CSF in 0/16 cases, representing in 'responders' a mean increase of 267% and 270% in the absolute number of NBT positive cells by rhuGM-CSF and rhuG-CSF, respectively. Morphological examination of cultured cells from 'responders', as compared to controls, showed decreased blast cell content but generally no evidence of terminal differentiation. The demonstration of Auer rods in NBT positive cells indicates that respiratory burst developed in a leukemic clone. These findings may be of physiological, pathophysiological and clinical relevance.
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PMID:Recombinant human colony stimulating factor-granulocyte/macrophage and -granulocyte, but not macrophage induce the development of a respiratory burst in primary human myeloid leukemic cells in vitro. 247 89

In February 1986, a 68-year-old woman was diagnosed as having acute myeloblastic leukemia (FAB-M1). At the time of diagnosis, 86.0% of the bone marrow cells were myeloblastoid, and 15% of these myeloblastoid cells were positive to myeloperoxidase. Surface marker analysis by flow cytometry disclosed granulocyte-associated antigen (MY7) and also lymphocyte-associated antigen (CALLA) on the leukemic cells. Chromosomal banding studies of bone marrow cells revealed trisomy 11 in 6 of 19 metaphases examined and normal karyotype in the others. Complete remission was attained after intensive combination chemotherapy, and has remained for 38 months. Only 19 patients with trisomy 11-associated acute nonlymphocytic leukemia (ANLL) including the present case have been reported. Morphologic analyses have revealed that the frequency of FAB-M1 is high. However, except for the present case, surface marker findings were apparent in only one M5a patient, in whom monocyte-macrophage-associated antigen was detected. Accordingly, careful surface marker studies will be needed to clarify the frequency of acute mixed lineage leukemia in such patients.
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PMID:[Trisomy of chromosome 11 in a case of common ALL antigen-positive acute myeloblastic leukemia (FAB-M1)]. 253 25

Interleukin-3 (IL-3) and granulocyte-monocyte-colony-stimulating factor (GM-CSF) stimulate proliferation of human acute myeloid leukemia (AML) in vitro, although patterns of response among clinical cases are diverse. Whether regulatory abnormalities related to growth factor responses in human AML may establish the outgrowth of the neoplasm is unclear. We determined receptor numbers and affinity for IL-3 and GM-CSF on human AML cells using human recombinant IL-3 (rIL-3) and GM-CSF (rGM-CSF). In 13 of 15 cases of primary AML high-affinity (kd 26 to 414 pmol/L) receptors for IL-3 were demonstrable on the cells. The average numbers of IL-3 receptors ranged from 21 to 145 receptors per cell. Normal WBCs showed IL-3 receptors on their surface at similar densities. IL-3 receptor positivity often correlated with GM-CSF receptor positivity of AML; GM-CSF receptors were demonstrated on the cells of 11 of 15 cases, although average numbers of GM-CSF receptors were ten times greater. The in vitro response of the cells to exogenous IL-3 or GM-CSF was examined by measuring thymidine uptake. Because IL-3 and GM-CSF were potent inducers of DNA synthesis in vitro, apparently relatively few receptors are required to permit activation of growth. These experiments did not provide evidence for overexpression or increased receptor sensitivity as an explanation for AML growth. In a minority of cases, however, the cells were unable to respond to IL-3 (four of 15 cases) or GM-CSF (four of 15 cases) despite normal receptor availability on the cell surface.
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PMID:Interleukin-3 and granulocyte-monocyte colony-stimulating factor receptors on human acute myelocytic leukemia cells and relationship to the proliferative response. 254 27

Retinoic acid receptor (RAR)-alpha mRNA expression was studied in a variety of myeloid leukemia cells with variable responsiveness to the induction of terminal differentiation by retinoic acid (RA). Cells from both the wild-type (wt), RA-responsive HL-60 promyelocytic leukemia cell line and a selected greater than or equal to 300-fold RA-resistant subline expressed approximately equal amounts of two RAR-alpha transcripts, 4.0 and 3.1 kb in size. In wt cells, the RAR-alpha did not change during induction of granulocyte differentiation by RA or macrophagic differentiation by 12-0-tetradecanoylphorbol-13-acetate (TPA). Relative to HL-60 cells, other cultured and fresh myeloid leukemia cells expressed 2.5-fold less to equal amounts of the RAR-alpha transcripts. The relative expression in six cases of acute promyelocytic leukemia (APL; two RA-responsive; one, previously treated with 13-cis-RA in vivo, equivocally RA-responsive) and one case of acute myelogenous leukemia (AML) with promyelocytosis (RA unresponsive) was 0.91 +/- 0.14 versus 0.53 +/- 0.14 for eight cases of nonpromyelocytic AML (p congruent to 0.001). Lymphoid leukemia cells expressed 2- to 5-fold less RAR-alpha mRNA. No qualitative variations in the mRNA transcripts were observed, although the 3.1 kb transcript was relatively decreased in three cases. The RAR-alpha gene was not amplified or detectably rearranged in any DNA source, although an apparent EcoRI restriction fragment length polymorphism was observed. It is concluded (a) that the steady-state level of RAR-alpha mRNA is not tightly correlated with natural responsiveness/unresponsiveness or, in some instances, acquired resistance to RA-induced differentiation and (b) that further studies are needed to determine if the mean 1.7-fold higher RAR-alpha mRNA level in APL cells could be an essential factor in the RA-responsiveness of APL cells, as primarily regulated at a different molecular level.
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PMID:Expression of retinoic acid receptor-alpha mRNA in human leukemia cells with variable responsiveness to retinoic acid. 255 72


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