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

Essential thrombocythemia (ET), one of the chronic myeloproliferative disorders, is a clonal disorder of multipotent stem cells. Although most patients with ET have a prolonged benign course, a minority of patients may develop a blastic crisis similar to chronic myelogenous leukemia (CML). A case of ET terminating in blastic crisis 8 years after the initial diagnosis is presented. The blast cells were cytochemically and immunophenotypically consistent with the acute myelogenous leukemia with minimal myeloid differentiation subtype of the FAB classification. From the review of the literature on blastic transformation of ET, acute leukemia with an M4 or M7 phenotype occurred more frequently. In addition, three valuable factors to predict the leukemic transformation of ET appear to be karyotypic abnormalities, such as involvement of chromosome 21, previous therapies with a mutagenic potential, and the capability of bone marrow cells to form in vitro spontaneous colonies as in CML.
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PMID:Essential thrombocythemia terminating in acute leukemia with minimal myeloid differentiation--a brief review of recent literature. 802 50

The ectoenzymes gamma-glutamyltransferase (gamma-GT) and the PIP2 phospholipid phospholipase-C (PLC), a second messenger generating enzyme active on the cytoplasmic membrane bilayer, were biochemically investigated in leukemic cells isolated from 67 patients with acute leukemia. Six groups were distinguished on the basis of morphology, cytochemistry and immunophenotyping according to the FAB classification: M0, M1-M2, M3, M4, M5 and CML blast crisis (CML-BC). The activity of PLC ranged from 0.6 to 14.5 nmol/min/mg without a significant difference among groups, whereas the gamma-GT activity varied significantly from 0 to 31.6 nmol/min/mg. The highest mean activity was measured in monoblastic leukemia (M5), followed by groups M4, CML-BC and M0 (undifferentiated) while the lowest activity was found in M1-M2 and M3 groups. Within each group, activity distribution profiles of both enzymes never correlated with each other, suggesting that in leukemic cells functional-structural constituents of both membrane leaflets were independently affected by the neoplastic process.
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PMID:Enzymes transducing extracellular signals in acute myeloid human leukemias. 809 82

Expression of the transcription factor GATA-1, which regulates several erythroid specific genes and possibly also some megakaryocytic genes, has been previously detected in normal erythroblasts, megakaryocytes, and basophils, and in some myeloid cell lines. It has been suggested that GATA-1 may be first expressed in a common progenitor and then further activated during erythroid-megakaryocytic and basophilic differentiation and repressed during myeloid maturation. We investigated GATA-1 mRNA expression in highly purified leukemic blasts representing different lineages and stages of myeloid differentiation and in a recently established leukemic cell line, GF-D8, which exhibits morphological, cytochemical and immunophenotypic characteristics of early myeloid progenitor cells. We found GATA-1 expression in five of five myeloid and in one megakaryocytic blast crisis of CML, in four of six cases of myelomonocytic leukemias (M4 according to FAB classification), in one case of erythroleukemia (M6), whereas lymphoid blast crisis of CML and all other FAB groups were completely negative. In addition, a low level of GATA-1 mRNA was also expressed by the GF-D8 cell line. These data further support the hypothesis that GATA-1 expression may occur not only in erythroid and megakaryocytic progenitors, but also in early myeloid progenitors, and then be further regulated during lineage-specific maturation.
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PMID:Expression of GATA-1 mRNA in human myeloid leukemic cells. 820 77

Owing to recent technical developments in automated hematology analyzers, identification of 5-part differential counts in white blood cells and also of abnormal leukocytes has become possible. Blood specimens from 200 patients with leukemic hematologic conditions were processed through a Coulter STKS which gives a favorable white cell differential count utilizing the following parameters: volumetric impedance (V), electric conductivity/cell volume (C), and a monochromatic laser beam which provides collectively white cell scatterplot (S). To analyze the presented figures of a pathologic scatterplot (SP) on the visual display unit, the standard scale derived from 220 normal SP patterns which was composed of four kinds of cell SP scales (neutrophil: N, monocyte: Mo, eosinophil: Eo, lymphocyte: Ly) was applied. Leukemic SP figures were variable depending upon both the type of FAB classification and their therapeutic processes. SP forms of M0-blasts were semi-round and located in the central area surrounded by N-, Mo-, and Ly-SP scale. Blast SP of M1 and M2 was shown as a developing process to the SP field containing immature myeloid cells extending from the central area. It was reasonable that immature neutrophilic SP expression was obtained in M3 and Ph1 positive CML. However, the SP of M3v and Ph1 negative CML showed myelomonocytic features as CMMoL does. Typical myelomonocytic SP patterns were obtained in M4 patients. SP figures of MDS were characterized by deformability, dislocation and another abnormality, and these changes, especially in lymphocytes are very useful for diagnosis of MDS. Therefore, the FAB subtype of AML including MDS and CML could be distinguished from each other on the basis of SP pattern. In lymphoproliferative disorders, limited conductivity in ALL-SP was characteristic, while irregular and deformed SP was peculiar in leukemic malignant lymphoma. It would be a valuable process to analyze the SP pattern obtained from an automated hematology analyzer for identification of leukemic diseases.
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PMID:[Hematological analysis of leukemic diseases using an automated hematology analyzer]. 829 37

We report two cases of Philadelphia chromosome (Ph)-positive acute leukemia with definite myeloid markers. Ph was the sole chromosomal abnormality at presentation, and neither eosinophilia, basophilia, thrombocytosis nor hepatosplenomegaly was present. In both cases, Ph+ myeloblasts showed positive stain for myeloperoxidase and naphthol ASD chloroacetate esterase, which fulfilled the FAB criteria of acute myelogenous leukemia (AML). Ph+ myeloblasts co-expressed myeloid and B-lymphoid antigens (CD10, CD13, CD19 and CD33). In case 1, myeloblasts rearranged M-BCR, and the expression of M-BCR/ABL chimeric RNA was demonstrated by using the reverse transcription polymerase chain reaction (RT-PCR). They also clonally rearranged IGH. Ph clone disappeared on cytogenetic analysis in remission, and granulocytes in remission did not have rearranged M-BCR. In case 2, morphocytochemically distinct myeloid and lymphoid blast populations were seen. Myeloblasts and lymphoblasts were enriched > 96% as CD19-/CD33+ and CD19+/CD33- populations, respectively. Both of them possessed the identical rearrangement of IGH and M-BCR, indicating a common leukemic progenitor cell origin. Furthermore, m-BCR/ABL was detected in addition to M-BCR/ABL on RT-PCR. Accordingly, both cases were diagnosed as de novo Ph+ acute leukemia rather than as chronic myelogenous leukemia in blastic crisis. Their mixed B-lymphoid/myeloid characteristics strongly suggest that so-called 'Ph+ AML' is derived from Ph+ myeloid/B-lymphoid stem cells.
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PMID:B-lymphoid/myeloid stem cell origin in Ph-positive acute leukemia with myeloid markers. 832 35

We analyzed active oxygen (hydroperoxide; H2O2) production by peripheral neutrophils in various hematological diseases by flow cytometry. One hundred microliters of heparinized fresh blood was sequentially incubated at 37 degrees C with 2',7'-dichlorofluorescein diacetate and with or without phorbol myristate acetate (PMA). After hemolysis, the pelleted white blood cells were subjected to flow cytometry, and the neutrophil fraction was gated on the cytogram. Production of H2O2 by the fraction was estimated by determining the increase in the relative intensity of fluorescence emitted from the fraction in response to stimulation by PMA. In controlled chronic myelogenous leukemia (CML) (WBC < 1 x 10(10)/1), H2O2 production was normal, while in uncontrolled CML (WBC > or = 1 x 10(10)/1), it was reduced. In myelodysplastic syndrome (MDS), H2O2 production was also reduced, but no significant difference was observed among FAB classification disease types in MDS patients. In untreated acute non-lymphocytic leukemia (ANLL), H2O2 production was reduced, while in the complete remission stage of ANLL, its level was normal, suggesting recovery from normal clones. In aplastic anemia, the H2O2 production level was normal. Steroid therapy might be responsible for the reduction of H2O2 production in non-Hodgkin's lymphoma and multiple myeloma. The production of H2O2 is closely related to the oxygen-dependent bactericidal activity of neutrophils, and, hence, can be utilized as an index to indicate susceptibility to infection. This neutrophil function can be determined easily in ordinary clinical facilities by using flow cytometry, and care should be taken to prevent infection when H2O2 production is reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Flow cytometric determination of active oxygen (hydroperoxide) produced by peripheral blood neutrophils in patients with hematological disorders. 836 85

Recent advances in molecular cytogenetics of leukemia is reported with special reference to the pathogenesis, diagnosis, prognosis, and potential gene therapy. Regarding leukemogenesis, we found that neocarzinostatin induced a variety of deletions and reciprocal translocations. Among these random chromosome abnormalities, two reciprocal translocations which were specific for certain leukemias could be observed; t(11;14)(q13;q32) and t(7;11)(p15p13). This fact suggests that a translocation carrying oncogene rearrangement may be of potential relevance to the leukemogenesis. The success in making a subgroup (FAB classification) identified a number of subtype-specific translocations in leukemias. It has been suggested that an initiation or progression-associated event is mediated through a gross chromosomal change. The molecular characterization of chromosomal rearrangement leads to the identification of genes involved in leukemia. Our recent works in molecular cytogenetics of chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL), FAB-M3 and -M4 were shown in this article. Since rearrangement of relevant genes were cloned, PCR made it feasible to detect minimal residual disease at 10(-6) level after intensive treatment or bone marrow transplantation for CML, Ph-positive ALL, M3 and approximately half of childhood leukemia. Recently developed fluorescent in situ hybridization (FISH) using specific probes can visualize certain chromosomes or chromosomal segments. Ph translocation, for instance, is now demonstrated as three spot-signals in interphase nuclei using YAC (yeast artificial chromosome)-BCR clone. Lastly, the use of antisense oligonucleotides for the BCR-ABL junctions should result in the inhibition of growth of CML clone. The strategy using antisense molecules may be very powerful tool in the gene-targeting therapy for human neoplasms.
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PMID:[Recent advances in molecular cytogenetics of leukemia]. 847 75

Correlation between the FAB classification and immunophenotype was studied in 169 consecutive adult patients with acute leukaemia (AL). The lineage of leukaemic cells could be determined in the majority of cases, whereas 3 patients (1.8%) remained unclassified. In 22 out of 71 patients (31%) with acute myeloid leukaemia (AML) FAB M1 and M2 types, and in 5 out of 16 patients (31%) with chronic myeloid leukaemia (CML) in myeloid blast crisis, leukaemic cells did not express myeloid lineage-related markers, indicating asynchronous expression of cell markers in a substantial proportion of patients. Flow cytometric two-colour immunofluorescence revealed mixed AL immunophenotype in 6 out of 169 patients (3.4%). This group included five CD2+AML (5% of AML tested) and one undifferentiated AL expressing CD10(CALLA), CDw65(VIM-2). The former group included FAB M1, M2, M3 and M4 forms of AML with a single cell population, and an AML M2 patient with both cytochemically and immunologically two separate populations of leukaemic cells. This further illustrates the heterogeneity of the target cell(s) for leukaemogenesis and the level of differentiation of AML cells. However, there was no difference in the treatment response and the remission duration between AML patients and patients with mixed phenotype AML.
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PMID:Correlation of morphological FAB classification and immunophenotyping: value in recognition of morphological, cytochemical and immunological characteristics of mixed leukaemias. 851 29

The FAB group has recently published guidelines for distinguishing chronic granulocytic leukaemia (CGL) from chronic myelomonocytic leukaemia (CMML) and atypical chronic myeloid leukaemia (aCML). Whereas CGL is generally recognized to be a distinct entity, there is debate as to whether CMML and aCML are separate disorders or part of a spectrum of myeloproliferative disorders with dysplastic features. Data are presented on 10 cases who developed features of a CML during the course of their disease but who presented with a normal or a low leucocyte count without a monocytosis and were diagnosed as refractory anaemia. This suggests that, at least in some cases, aCML represents an unusual evolution of MDS, and even though these patients have a uniformly poor prognosis it may be premature to regard aCML as a distinct clinical entity.
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PMID:Atypical chronic myeloid leukaemia, a distinct clinical entity related to the myelodysplastic syndrome? 861 21

Microsatellites are highly polymorphic, short-tandem repeat sequences dispersed throughout the genome. Instability of these repeat sequences at multiple gentic loci may result from mismatch repair errors and occur in hereditary nonpolyposis colorectal cancer and several other sporadic cancers, including chronic myelocytic leukemia as it progresses to blastic crisis. We investigated whether genetic instability occurred as myelodysplasia progressed to acute myelocytic leukemia. To this end, we studied microsatellite instability in 20 patients with myelodysplastic syndrome (MDS). These included five patients with refractory anemia (RA), three with refractory anemia with ringed sideroblast (RARS), nine with refractory anemia with excess blasts (RAEB) and three with chronic myelomonocytic leukemia (CMML). All of these patients transformed to acute myelocytic leukemia (AML) of various subtypes: three patients with M1, 11 with M2 and six patients with M4 (according to FAB classification). The DNA from both the MDS and AML phases of their disease was analyzed at 16 loci, and only four microsatellite instabilities were found in the 240 paired samples (1.6%) analyzed. These results indicate that mismatch repair errors such as microsatellite instability are not important in the evolution of MDS to AML.
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PMID:Infrequent microsatellite instability during the evolution of myelodysplastic syndrome to acute myelocytic leukemia. 862 9


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