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)

The effects of competitive inhibition of hydroxymethylglutaryl coenzyme A (HMG CoA) reductase by compactin on the in vitro proliferation of peripheral blood myeloid leukemia cells were studied using the cells from 45 patients with acute myeloid leukemia or chronic myelogenous leukemia in blast phase. The cells from 58% of these patients showed a dose-related inhibition of DNA synthesis when incubated with compactin. Unexpectedly, cells from 18% of the patients were resistant to the inhibitory effects of compactin on DNA synthesis and responded to the HMG CoA reductase inhibition with an actual increase in the incorporation of 14C-labeled thymidine into DNA. Another 18% of the patients studied displayed both inhibition and stimulation of DNA synthesis in a biphasic response depending on the particular concentration of compactin used. The maximum enhanced rates of cellular DNA synthesis were observed with lower compactin concentrations (5 x 10(-7) mol/L) than were required for maximum inhibition of DNA synthesis (10(-5) mol/L). Leukemia cells displaying a stimulated response to compactin had a significantly lower baseline DNA synthetic rate than did cells that showed an inhibitory response of DNA synthesis to compactin. There was no correlation between these cells' varying DNA synthetic response to compactin and measures of baseline HMG CoA reductase activity or acetate conversion to cholesterol. Whereas the observation of cellular DNA synthesis stimulation by HMG CoA reductase inhibition has not been observed in other mammalian cells and seems paradoxical, explanations may emerge in light of our growing knowledge concerning the importance of isoprenylation for the function of certain cell regulatory proteins.
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PMID:Inhibition of hydroxymethylglutaryl coenzyme A reductase activity induces a paradoxical increase in DNA synthesis in myeloid leukemia cells. 199 91

We investigated m-AMSA or doxorubicin (Dx) induced DNA single-strand breaks (DNA-SSB) in myeloid leukemia cells obtained from 8 adult patients suffering from AML. Highly purified AML cells were stimulated to proliferate with the addition of the appropriate growth factor (GCT) and exposed to different concentrations of m-AMSA or Dx for 1 or 4 h, respectively. DNA-SSB were determined by alkaline elution techniques. Either the kinetics or the amounts of DNA-SSB caused by both topoisomerase II inhibitors were variable among different cases. By increasing m-AMSA concentrations there was a concomitant increase in DNA-SSB up to a plateau at the highest concentrations. Dx induced DNA-SSB followed a bell shape curve with a decrease in the number of breaks at the highest concentrations that was evident in most cases. The interindividual variability of Dx-induced DNA-SSB was not correlated with intracellular Dx concentrations as assessed by flow cytometry. No correlation was evident between the amount of DNA breaks induced by m-AMSA and that induced by Dx. These data suggest that AML cells derived from different patients are not necessarily cross-sensitive or cross-resistant to topoisomerase II inhibitors with different chemical structures such as amsacrine or anthracyclines.
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PMID:Doxorubicin and m-AMSA induced DNA damage in blast cells from AML patients. 199 42

The genomic sequencing technique has been applied to assess the state of methylation in the DNA from human leukocyte subpopulations from healthy individuals and in the DNA from several individuals with myeloid or lymphatic leukemias or non-Hodgkin lymphomas. Leukocyte populations were purified by the high-gradient magnetic cell sorting technique. In the human tumor necrosis factor alpha (TNF-alpha) gene segment between nucleotides 300 and 1150, the specific methylation profile in the DNA from human granulocytes and monocytes is maintained in three cases of myeloid leukemia. In one such case, all 5-methyl-2'-deoxycytidine residues have been replaced by cytidine. In a chronic lymphatic T-cell leukemia, all 5-methyl-2'-deoxycytidine residues have been substituted by cytidine. In normal B lymphocytes, in two cases of chronic lymphatic B-cell leukemias and two cases of non-Hodgkin lymphomas, all 5'-CG-3' sequences in this gene segment are devoid of methylation. In the TNF-beta gene, DNA methylation is decreased in several examples of acute or chronic myeloid leukemias in comparison to normal human granulocytes or monocytes, whose DNA is almost completely methylated between nucleotides 700 and 900. In human T and B lymphocytes, the main producers of TNF-beta, in three instances of chronic lymphatic leukemias and two cases of non-Hodgkin lymphomas, all 5'-CG-3' sequences are unmethylated in this region. The DNA from the human HeLa cell line is highly methylated at all 5'-CG-3' sequences in the TNF-alpha and -beta genes. The TNF-alpha gene is transcribed in the cells of one case of acute myeloid leukemia in which the analyzed region of the TNF-alpha gene is completely unmethylated. The TNF-beta gene is not transcribed in any of the malignant cells tested.
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PMID:DNA methylation profiles in the human genes for tumor necrosis factors alpha and beta in subpopulations of leukocytes and in leukemias. 206 56

The mechanisms that are involved in the control of the normal differentiation of hematopoietic progenitor cells are largely unknown. Moreover, little is known concerning the types of genes that can alter the ability of hematopoietic progenitors to differentiate and cause transformation. One approach to the latter has been to use retroviral induced IL-3-dependent myeloid leukemia cell lines to identify transforming genes by their activation through insertional mutagenesis. This approach has implicated alterations in c-myb in transformation and has identified a novel transcriptional factor of the zinc finger family that is frequently activated in murine myeloid leukemias and in some cases of human AML. Using this approach it should be possible to identify additional myeloid transforming genes. The identification and characterization of the genes will provide important information and approaches to the study of the regulation of differentiation in normal hematopoiesis.
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PMID:Insertional mutagenesis and transformation of hematopoietic stem cells. 216 32

The effects of TPA (12-0-tetradecanoylphorbol-13-acetate) and RA (retinoic acid) were investigated on the cell lines HL60 (acute promyelocytic leukemia) and K562 (erythroleukemia) and on cells from patients with several kinds of leukemia. There were 14 cases of acute lymphocytic leukemia (ALL), 2 cases of chronic lymphocytic leukemia (CLL), 23 cases of acute myeloid leukemia (M1-M7), 5 cases of chronic myelocytic leukemia in blast crisis (CML-BC) and 2 mixed leukemias. In almost all of the cases examined, after TPA exposure cells from patients with proven myeloid leukemia became adherent to the substrate, while lymphoid leukemia cells remained in suspension, allowing the differentiation of lymphoid from myeloid blasts. The only exception was in one case of CLL, which had cells that became adherent with long filamental projections. In addition, increased phagocytosis following TPA exposure permitted characterization of M7 as this was the only myeloid leukemia negative for phagocytosis. Further discrimination between the subtypes of myeloid leukemia could be based on the increased lysozyme production seen after TPA in M4 and M5. Esterase positivity allowed the discrimination of M1 cells, which were negative before and after TPA treatment. In agreement with the results of other authors, TPA and RA led to independent ways of differentiation, granulocytic-like lineage and monocytic-like cells being favored by RA and TPA, respectively. The capacity of the same cell to differentiate into more than one lineage, depending on whether RA or TPA was used, was only seen in the present study with M3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myeloid leukemia differentiation by phorbol ester and retinoic acid: a practical approach. 223 Nov 80

Conditioned medium from mitogen stimulated normal peripheral blood lymphocytes (PBL) has been demonstrated to contain a maturation inducer activity mediating the differentiation of human myeloid leukemia cells to monocytes and macrophages. The maturation inducer activity was isolated by salt precipitation, Sepharose CL-6B ion exchange and affinity chromatographies and electrophoresis. Two separate activities with M.W. ranges of 52-56 and 32-35 kDa capable of mediating the terminal differentiation of leukemic HL-60 promyelocytes to monocytes and macrophages were detected. The higher molecular weight species was determined to be a 54 kDa single polypeptide and was found to be distinct from IL-3 and IL-6 by ELISA and differentiation blocking assay. The inducing activity of the 32-35 kDa material was largely neutralized after treatment with anti-IL-3, but not with other antibodies. Employing the immunofluorescent antibody technique, the 54 kDa protein was detected on the surface membranes of PBL. The proportions and number of maturation inducer bearing lymphocytes in patients with acute myelogenous leukemia (0.4% and 35/mm3, respectively) were significantly lower than that of healthy donors (7.9% and 178/mm3) The role of these physiological factors in leukemia cell differentiation is discussed.
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PMID:Two separate differentiation inducing proteins for human myeloid leukemia cells and their isolation from normal lymphocytes. 223 10

Although otologic involvement by leukemic infiltration was supposed to be unusual, increasing number of cases have been reported in recent years, probably due to the advance of chemotherapy, improved remission rate and longer survival of leukemic patients. Two cases of myelogenous leukemia with infiltration of mastoid bone were reported. One is 15-year-old girl with acute myelogenous leukemia, which had been well controlled for 1 year, developed a sudden onset of facial nerve palsy. The other is 30-year-old female with chronic myelogenous leukemia and blastic crisis, complained hearing loss. As both cases had exudate in the tympanic cavity, the punctures were carried out through the eardrum. The pathological study of these exudate cells revealed the involvement of mastoid bone by leukemia. The cytologic examination of exudate in the tympanic cavity is simple, time-sparing and of little burden to the patient. This technique is very useful and supposed to take the place of the exploratory surgery of mastoid cavity which is previously considered necessary for the correct diagnosis.
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PMID:[Leukemic infiltration of the mastoid bone--cytologic examination of exudate in the tympanic cavity as a useful diagnostic method]. 225 6

We studied the effect of mitoxantrone (MIT) on the proliferation and differentiation of murine myelomonocytic leukemia cell line WEHI-3B (D+), human myelocytic leukemia cell line HL-60 and cells from patients with newly diagnosed acute nonlymphocytic leukemia (ANLL). In a liquid culture, growth inhibition and differentiation of WEHI-3B (D+) cells to mature myeloid cells and a reinforcement tendency of the induction of nitroblue tetrazolium reducing capacity as well as of ASD chroloacetate esterase staining was observed by the treatment with MIT. Fresh ANLL cells classified as M4 were induced by MIT to undergo terminal differentiation to macrophage-like cells. Since at concentrations of WEHI-3B (D+) cells of less than 1 x 10(5)/ml induction of differentiation was observed due to MIT, it is suggested that its mechanism of action differs from that of the induction of differentiation by granulocyte colony-stimulating factor and is due to the direct action of MIT.
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PMID:[Induction of differentiation of myelomonocytic leukemia cells by mitoxantrone]. 225 55

Human myeloid cell nuclear differentiating antigen (MNDA) is a Mr 55,000 non-histone basic nuclear protein expressed in myeloid leukemia cell lines that are at late stages of differentiation (HL-60 and U937) and in normal granulocytes and monocytes, but is not present in lymphoid cells or in other human cells and tissues tested. Affinity purified monospecific polyclonal antibodies and rat monoclonal antibodies have been developed for the immunocytochemical detection of MNDA. Using these antibodies, we surveyed 21 cases of acute leukemia classified by French-American-British (FAB) Group criteria, two cases of biphenotypic acute leukemia and one case of blast crisis of chronic granulocytic leukemia for the presence of MNDA. The most intense staining reactions were present in the nuclei of two cases of acute promyelocytic (FAB M3) leukemia. MNDA was not detected in three of five cases of acute myeloblastic leukemia without maturation (FAB M1). The remaining two cases of the M1 category showed weak to moderate staining. No staining reaction was seen in acute lymphocytic leukemia (ALL), biphenotypic leukemia or the lymphoid blast crisis of chronic granulocytic leukemia. Variable staining reactions were demonstrated in the remaining cases. These data suggest that the presence of MNDA is correlated with myeloid and monocytic differentiation in acute leukemia, being strongly expressed in M3 type, often not detected in M1 leukemia and absent in ALL.
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PMID:Expression of human myeloid cell nuclear differentiation antigen (MNDA) in acute leukemias. 225 28

Fifteen bone marrow autotransplants (BMAT) in patients with acute myeloblastic leukemia (AML) were performed after the first remission. The mean age was 37 years (range 12 to 60 years). According to the morphological classification FAB, 8 patients had monocytic leukemia (M4, M5) and 7 myeloid leukemia (M1, M2, M3). The mean interval elapsed between the date of complete remission and the BMAT was 3.9 months (range 1 to 5-9 months). In 8 patients this interval was longer than 6 months and in 7 cases it was shorter than 6 months. After achievement of the complete remission all patients underwent certain cycles of intensification before the BMAT. Eight patients received only a cycle whereas 7 patients received more than one cycle (between 2 and 4). The conditioning protocol consisted of cyclophosphamide (CP) (60 mg/kg x 2) and total body radiotherapy (TBR) (10 Gy) in 9 patients; CP and busulfan in five; and CP, cytarabine at high doses and melphalan in one case. Marrow extraction was performed after completion of chemotherapy of intensification. In 5 cases the bone marrow was depleted of leukemic cells by previous in vitro treatment with ASTA-Z. There are at present 8 alive patients. The survival free of illness was 51.8%. Seven patients died: 3 cases because relapse of the leukemia, 3 due to attachment failure of the transplantation, and one patient suffered a viral myocarditis. The survival free of illness was significantly longer in those patients transplanted after 6 months of the complete remission.
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PMID:[Bone marrow autotransplantation in patients with acute myeloblastic leukemia in primary remission]. 228 Jun 16


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