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)

Three cases of megakaryoblastic transformation of chronic granulocytic leukemia (CGL) are reported. In each case, the leukemic transformation had morphologic features suggesting megakaryocytic differentiation. This was confirmed by positive immunostaining with a monoclonal antibody (HP1-1D) specific for platelet and megakaryocyte glycoprotein IIb/IIIa antigen, which was expressed by the majority of the leukemic blasts in all three cases. Cases with evidence of multilineage differentiation of the leukemic transformation were excluded. A striking feature in two patients was the manifestation of lytic bone lesions and soft tissue masses at presentation. A biopsy of a lytic bone lesion and soft tissue mass in one patient revealed a megakaryoblastic leukemic infiltrate, which by immunocytochemical staining was positive for the megakaryocytic markers, glycoprotein IIb/IIIa antigen, and Factor VIII (von Willebrand factor) antigen. In contrast to granulocytic sarcomas, the megakaryoblastic sarcoma did not stain cytochemically for chloroacetate esterase. The mean survival after acute transformation was 5.3 months. The three cases of megakaryoblastic transformation represented a significant proportion of all CGL blastic transformation cases (ten cases) evaluated by bone marrow examination in our institution during a 13-month period. Megakaryoblastic transformation of CGL may occur more frequently than has been appreciated, and can present as lytic bone lesions or as soft tissue megakaryoblastic sarcomas.
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PMID:Megakaryoblastic transformation of chronic granulocytic leukemia. 243 83

To characterize molecular mechanisms operating in chronic myeloid leukemia (CML) cells with a view toward development of novel therapeutic targets, we analyzed gene-expression profiles of cancer cells from 27 CML patients using a cDNA microarray representing 23,040 human genes. By comparing expression patterns of CML with those of normal cells, we identified 150 genes that were commonly highly up-regulated in CML cells. In addition to 54 genes (34 of them ESTs) whose functions are currently unknown, the up-regulated elements included genes encoding cell-cycle regulators, transcriptional activators, transcriptional factors, and protein kinases as well as proteins already known to be induced in CML, such as some hemoglobins, haptoglobin (HP1), and matrix metalloproteinase 9 (MMP-9), a protein involved in tissue remodeling and tumor invasion. On the other hand, our protocol selected 106 genes, including 13 of unknown function, as being commonly significantly down-regulated in all phases of CML. The results of semiquantitative RT-PCR experiments with 11 representatives of the up-regulated group supported the reliability of our microarray analysis. These data should provide useful information for finding candidate genes whose products might serve as molecular targets for treatment of CML patients.
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PMID:Genome-wide analysis of gene-expression profiles in chronic myeloid leukemia cells using a cDNA microarray. 1288 4

We show that common heterochromatin antigenic protein markers [HP1alpha, -beta, -gamma and mono-, di-, and trimethylated histone H3 lysine 9 (H3K9)], although present in human blood progenitor CD34+ cells, differentiated lymphocytes, and monocytes, are absent in neutrophil granulocytes and to large extent, in eosinophils. Monomethylated and in particular, dimethylated H3K9 are present to variable degrees in the granulocytes of chronic myeloid leukemia (CML) patients, without being accompanied by HP1 proteins. In patients with an acute phase of CML and in acute myeloid leukemia patients, strong methylation of H3K9 and all isoforms of HP1 are detected. In chronic forms of CML, no strong correlations among the level of histone methylation, disease progression, and modality of treatment were observed. Histone methylation was found even in "cured" patients without Philadelphia chromosome (Ph) resulting from +(9;22)(q34;q11) BCR/ABL translocation, suggesting an incomplete process of developmentally regulated chromatin remodeling in the granulocytes of these patients. Similarly, reprogramming of leukemia HL-60 cells to terminal differentiation by retinoic acid does not eliminate H3K9 methylation and the presence of HP1 isoforms from differentiated granulocytes. Thus, our study shows for the first time that histone H3 methylation may be changed dramatically during normal cell differentiation. The residual histone H3 methylation in myeloid leukemia cells suggests an incomplete chromatin condensation that may be linked to the leukemia cell proliferation and may be important for the prognosis of disease treatment and relapse.
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PMID:Methylation of histones in myeloid leukemias as a potential marker of granulocyte abnormalities. 1550 73