Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biochemical activities of 8 lysosomal acid hydrolases in leukemic cells from 48 patients were examined. Characteristic alterations were found in alpha-mannosidase, beta-galactosidase and N-acetyl-beta-glucosaminidase activities of leukemic cells. The level of alpha-mannosidase activity was much higher in myelo(mono)genous leukemias (AML, AMoL, AMMoL, CML and CMMoL) than in lymphogenous ones (ALL, T-cell leukemia, hairy cell leukemia and CLL) without exception. The beta-galactosidase activity also differed as a result of alpha-mannosidase, except in T-cell leukemia. In T-cell leukemia it was within the range of normal lymphocytes, but in the other lymphogenous leukemias it was significantly below normal. N-acetyl-beta-glucosaminidase activity in myelo(mono)genous leukemic cells was above the range of normal granulocytes. The changes in these enzyme levels were consistent. The lymphocytic or myelocytic nature of three cases of acute undifferentiated leukemia could be determined by enzyme studies. In two cases it was lymphocytic and in one it was myelocytic. The enzymatic abnormalities were also found in morphologically mature neutrophils from patients but not only chronic types (CML, CMMoL) but also acute types (AMoL, AMMoL) of leukemias, and were similar to those of their respective leukemic cells. Analysis of lysosomal enzymes (at least three of those mentioned above), can elucidate one of the biochemical properties of leukemic cells and may be valuable in the differentiation of leukemias.
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PMID:Biochemical activities of lysosomal acid hydrolases in leukemic cells. 694 81

Leukemic cells from the peripheral blood of 52 patients with acute and chronic leukemias were incubated with 12-0-tetradecanoyl phorbol ester (TPA). Thirty-one cases of lymphocytic leukemia (18 cases of acute lymphoblastic and 13 cases of chronic lymphocytic leukemia), 13 cases of acute nonlymphoblastic (myelo or myelomonoblastic) leukemia, and eight cases of blastic crisis of CGL (seven cases of predominantly myeloblastic crisis, and one case of lymphoblastic crisis) were studied. In all cases of lymphoid leukemia, cells formed clumps or aggregates after exposure to TPA, while in all cases of myeloid leukemia cells became adherent to the substrate. Seven of the eight cases of blastic crisis of CGL were predominantly myeloid in type and cells adhered to the substrate, while in a single case of lymphoid crisis in CGL cells formed clumps after TPA exposure. Functional, cytochemical, and ultrastructural studies showed altered cell differentiation and continuing in vitro maturation of leukemic cells after exposure to TPA. In the light of the above results, it is concluded that this simple test employing TPA exposure in vitro serves as a reliable means of distinguishing blasts from different origins in human leukemias.
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PMID:Exposure to phorbol diester (TPA) in vitro as an aid in the classification of blasts in human myelogenous and lymphoid leukemias: in vitro differentiation, growth patterns, and ultrastructural observations. 696 Jun 90

In the last decade, specific chromosomal abnormalities were found in leukemic cells in children, which had diagnostic or even prognostic significance. Adult type chronic myeloid leukemia is associated with the Philadelphia chromosome (Ph1, t(9;22)), acute myeloid leukemia with maturation with t(8;21), acute promyelocytic leukemia with t(15;17), (myelo)-monocytic leukemia with abnormalities of chromosome II, and acute monoblastic leukemia with t(9;11). B-cell acute lymphocyte leukemias are associated with a t(8;14) or some other t(8q); in the other forms of acute lymphocytic leukemias a t(4;11) or 6q- is sometimes found. The presence of a t(8;21) seems to be associated with a better prognosis. In lymphocytic leukemias the presence of 50 or more chromosomes seems to predict a favourable prognosis, while, on the contrary, the presence of any translocation indicates a grave prognosis.
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PMID:[Chromosome abnormalities in leukemia in children. Occurrence and clinical significance]. 696 36

A 77-year-old man, in whom chronic myeloid leukemia (CML) had been diagnosed in October 1990, was admitted to hospital with right chest pain in November 1992. Bone marrow examination revealed the chronic phase of CML. Chest X-ray showed right pleural effusion. The cells from pleural effusion were positive for CD7, CD13, CD33, CD41a, including CD33, CD41a-double positive cells in 57.5%. Southern blot analysis revealed 3'bcr rearrangement. Electron microscopic examination showed the presence of platelet peroxidase. An abnormal karyotype with various additional chromosomes was observed. This is a rare case of extramedullary pleural myelo-megakaryoblastic biphenotypic crisis during the chronic phase of CML.
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PMID:[Extramedullary pleural myelo-megakaryoblastic crisis during hematological chronic phase in chronic myeloid leukemia]. 813 19

There is evidence to suggest that the p120 GAP (GAP), originally described as an inhibitor of p21ras, may also serve as a downstream effector of ras-regulated signal transduction. To determine whether GAP expression is required for the growth of human normal and leukemic hematopoietic cells, we used GAP antisense oligodeoxynucleotides to inhibit it and analyzed the effects of this inhibition on the colony-forming ability of nonadherent, T lymphocyte-depleted mononuclear cells and of highly purified progenitors (CD34+ MNC) obtained from the bone marrow and peripheral blood of healthy volunteers or chronic myeloid leukemia (CML, bcr-abl-positive) patients. The acute myelogenous leukemia cell line MO7, the Philadelphia BV173 cell line, and the acute promyelocytic leukemia NB4 and HL-60 cell lines were similarly examined. GAP antisense treatment inhibited colony formation from normal myelo-, erythro-, and megakaryopoietic progenitor cells as well as from CML progenitor cells. Proliferation of MO7 (growth factor-dependent) and BV173 (bcr-abl-dependent) cells, but not that of NB4 and HL-60 (growth factor-independent) cells, was also inhibited, even though a specific downregulation of GAP was observed in each cell line, as analyzed by either or both mRNA and protein expression. Stimulation of MO7 cells with hematopoietic growth factors increased the expression of GAP as well as the levels of active GTP-bound p21ras. Stimulation of GAP expression was inhibited upon GAP antisense treatment. These data indicate that p120 GAP is involved in human normal and leukemic hemopoiesis and strongly suggest that GAP is not only a p21ras inhibitor (signal terminator), but also a positive signal transducer.
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PMID:p120 GAP requirement in normal and malignant human hematopoiesis. 824 73

We report a 19-year-old female with blastic transformation of chronic myelogenous leukemia whose blasts had CD33 and CD4 phenotypes, although no significant characteristics were detected by morphological and histochemical analysis. In a colony assay with hematopoietic growth factors, the blasts proliferated and differentiated into myelo-monocytic lineage, particularly in the presence of GM-CSF or IL-3 + G-CSF. The blasts transformed from CML were assumed to be myelo-monocytic progenitor cells, corresponding to GM colonies. Blastic transformation expressing such a phenotype has not been reported previously.
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PMID:CD33, CD4-double positive blastic transformation in a patient with chronic myelogenous leukemia. 836 89

Fourteen patients with high-risk leukemia (six with relapsed AML, three with relapsed ALL, one with AML-M0, four with CML in myeloid blastic crisis) were treated with a combination chemotherapy of carboplatin (200-300 mg/m2/day) and cytosine arabinoside (100 mg/m2/day) by 24 h continuous infusion for 5-7 days. Five patients (35.7%) achieved complete remission including two patients complicated with myelofibrosis (one with AML-M0 and one with CML in myelo-megakaryocytic crisis). Thirteen patients had nausea and vomiting, five patients had severe, prolonged neutropenia for which it was necessary to administer granulocyte colony-stimulating factor and six patients had severe thrombocytopenia. We concluded that this regimen is effective for the treatment of high-risk leukemia.
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PMID:Combination chemotherapy of carboplatin and cytosine arabinoside for high-risk leukemia: a pilot study. 863 58

Chronic myelogenous leukemia (CML) is a myelo-proliferative disorder which, after a chronic phase which lasts an average of 3 years, evolves into an acute disease which is resistant to chemotherapy. Nevertheless, a few studies have reported cases in which partial or complete hematologic, cytogenetic and/or molecular remission of the disease were observed either spontaneously or after non intensive chemotherapy, with or without medullar aplasia. Some of these patients later relapsed into a blast crisis. We report a case of CML with clinical and hematologic remission for 19 years after two cycles of busulphan not causing medullar aplasia, negative for the BCR/ABL gene by Southern blot but with the gene's mRNA detectable by hot start nested RT-PCR.
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PMID:Detection of bcr/abl mRNA in a case of chronic myelogenous leukemia in long-term remission: CML or sensitivity of detection? 979 59

Bone marrow features in stable-phase chronic myelogenous leukemia (CML) are characterized by a striking heterogeneity which is determinable by appropriate means including representative pre-treatment trephine biopsies, immunohistochemistry and morphometry. Cell lineages involved to a variable extent consist not only of neutrophil granulopoiesis, but include also megakaryocytes, erythroid precursors, resident macrophages and lymphocytes. Moreover, the stromal compartment, in particular reticulin and collagen fibers, plays a pivotal role in the disease process. Following morphometric analysis significant correlations may be calculated between histological parameters and clinical-laboratory findings. Relevant interactions are detectable between number of megakaryocytes and their precursors with fiber density. This findings is in line with the close functional relationships between megakaryopoiesis and fibroblasts regarding the complex pathomechanisms of myelofibrosis. Moreover, other correlations are observable between reduction of erythropoiesis or increase in fibers with clinical features like anemia, percentages of myelo- and erythroblasts in the peripheral blood, spleen size or LDH level. These variables are in keeping with more advanced stages of CML which indicate a transition to myeloid metaplasia and thus exert a significant impact on survival. Consequently, the different risk profiles of patients are determined by both clinical and morphological parameters of predictive value. Regarding the latter, extent of myelofibrosis, amount of erythroid precursors and numbers of myeloerythroblasts in the peripheral blood are significantly associated with prognosis. For this reason, it should be mandatory to enter morphological criteria into prospective clinical trials on CML, not only for diagnostic purpose, but also for a proper evaluation of different survival patterns.
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PMID:Bone marrow histopathology in chronic myelogenous leukemia (CML)--evaluation of distinctive features with clinical impact. 1050 40

An immunohistochemical and morphometric study was performed on bone marrow biopsies in 604 patients with chronic myelogenous leukemia (CML) to compare morphological and clinical features and to evaluate effects of interferon (IFN) and chemotherapy. Following morphometry significant correlations were calculated between number of CD61(+) megakaryocytes, including their precursors with fiber density. This finding is in line with the close functional relationship between megakaryopoiesis and fibroblasts regarding the complex pathomechanism of myelofibrosis. The latter was observed in about 28% of patients already at diagnosis. In a similar way, the frequency of CD68(+) macrophages was correlated with the amount of Ret40f(+) nucleated erythroid precursors, implicating an involvement of this cell lineage in iron turnover, hemoglobin synthesis, and degradation of the expelled nuclei from normoblasts. The (alpha-D-galactosyl residue-expressing) Pseudo-Gaucher cells were detectable in 30% of pretreatment specimens. Moreover, significant associations were calculable between reduction in erythropoiesis or increase in fibers with clinical features such as hemoglobin level, percentages of myelo- and erythroblasts in the peripheral blood, and spleen size. These variables are in keeping with more advanced stages of CML. Based on our morphometric evaluations, a classification into three different histological subgroups: granulocytic, megakaryocytic, and myelofibrotic was carried out. This simplified staging system was correlated with corresponding sets of hematological data. Sequential biopsies in 173 patients with monotherapy by IFN, hydroxyurea (HU), or busulfan (BU) revealed a fibrogenic effect of IFN in contrast to a fiber-reducing property of HU. The dynamics of myelofibrosis and changes of major cell lineages during treatment were readily demonstrable by calculating corresponding indices. These included the ratios between quantitative differences of corresponding variables at repeated examinations and time. Thus, in patients with complete hematological remission following IFN administration, regeneration of erythropoiesis was found to be accompanied by an increase in the total number of CD68(+) macrophages, including activated subpopulations. Histological subgroups showed a transition from a (nonfibrotic) granulocytic and megakaryocyte pattern to the myelofibrotic subtype in about 40% of patients. This change was opposed to a numerical reduction in the myelofibrotic subtype which occurred in 17 patients (36%), but predominantly in those under HU therapy. In conclusion, the striking heterogeneity of bone marrow features in CML warrants a careful morphological evaluation of trephine biopsies and appropriate means of processing to achieve relevant correlations with clinical data and, thus, allows a more elaborate insight into the dynamics of the disease process.
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PMID:[Histologic and hematological findings in CML. A comparative immunohistochemical-morphometric and clinical study on bone marrow biopsies from 604 patients derived from two institutes of pathology (Cologne/Freiburg)]. 1066 68


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