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)

In 55 patients with Ph1+ CML under interferon (IFN) monotherapy, an immunohistochemical and morphometric study on pretreatment bone marrow biopsies was performed to evaluate the prognostic impact of clinical as well as histological disease features. For identification of megakaryocytes we used the PAS stain and CD61 to calculate the subfraction of precursors (pro- and megakaryoblasts). Demonstration of macrophages and their different subsets was carried out by PG-M1 (CD68) and the GSA-1 lectin. The erythroid precursors were stained by Ret40f (anti-glycophorin C). Density of argyrophilic (reticulin plus collagen) fibers was determined by applying Gomori's silver impregnation method. Clinical variables like state of hematological response to IFN administration, age, spleen and liver size, myeloblasts plus promyelocytes, basophils as well as basophils and eosinophils exerted a predictive capacity by univariate statistical analysis. However, when entering these factors into previously published risk models, i.e., the so-called Sokal score and its modifications, to assess subgroups with different survival patterns or relative risk groups, a clear-cut discrimination was not feasible. Bone marrow features of prognostic value consisted of megakaryocytes and their precursors, fibers, and pro- and erythroblasts. Only when including histological variables into a formerly reported Cox model, could a significant separation of patients into the different categories or relative risk groups be computated. In conclusion, the present data emphasize the prognostic impact of histological parameters to be considered in all clinical trials on CML.
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PMID:Clinical and histological features retain their prognostic impact under interferon therapy of CML: a pilot study. 754 52

An immunohistochemical and morphometric analysis was performed on trephine biopsy specimens in 60 patients with chronic myeloid leukemia (CML) to quantify erythropoiesis and its proliferation capacity and to assess the stainable marrow iron (hemosiderin). For this purpose, an elaborate double-immunostaining technique was applied. This included a monoclonal antibody (PC10) that is directed against proliferating cell nuclear antigen (PCNA), followed by an antibody against glycophorin C (Ret40f), to identify all nucleated erythroid precursor cells. Additionally, morphometric data were derived from immunostaining of megakaryocytes (CD61) and macrophages (PG-M1), including its hemosiderin-laden subpopulation. Finally the determination of argyrophilic (reticulin) fiber density was carried out. In comparison with a control group (15 patients) without any hematologic disorder, in CML patients morphometric evaluation showed a significant reduction in the number of erythroblasts and normoblasts. This feature was associated with a PCNA-labeling index within the normal range and a decreased stainable marrow iron (number of hemosiderin-storaging macrophages). Several parameters were established to exert a predictive value on survival. A worsening of prognosis was associated with a decrease in the number of erythroid precursors (< 460/mm2), a low hemoglobin level (< 10 g/dl), a high megakaryocyte count (> 50 cells/mm2), an increased density of reticulin fibers (> 30 i x 10(2)/mm2) and splenomegaly (> 15 cm below costal margin). Our findings are in keeping with results obtained from in vitro studies of cell proliferation in CML, which is not significantly altered in comparison with the normal bone marrow. Finally, the present data, although derived from a small group of patients, emphasize the impact of histologic variables to be included in one of the major clinical trials on prognosis in CML.
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PMID:Erythropoiesis in CML--immunomorphometric quantification, PCNA-reactivity, and influence on survival. 790 86

Human p55, the major palmitoylated protein associated with the cytoplasmic face of the erythrocyte membrane, is believed to modulate interactions between protein 4.1 and glycophorin C. It is the prototype of a newly described family of signaling molecules that includes hD1g, the human homologue of the Drosophila discs-large tumor suppressor protein. Chronic myeloid leukemia is characterized by transformation to a fulminating acute leukemia, heralded by evolution of the Philadelphia chromosome positive genotype (Ph +) to further abnormalities. RT-PCR of p55 mRNA from a patient with acute megakaryoblastic CML revealed a 69 base pair deletion in the PDZ domain, corresponding to exon 5 of the p55 gene. The deletion of constitutive exon 5 not only marks the first abnormality of the p55 cDNA in human disease but also the first abnormality of a PDZ domain in human disease and may represent another genetic abnormality associated with CML in blast crisis.
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PMID:Exon skipping truncates the PDZ domain of human erythroid p55 in a patient with chronic myeloid leukemia in acute megakaryoblastic blast crisis. 1007 Oct 76

A multicenter, immunohistochemical and morphometric study was performed on diagnostic pretreatment bone marrow biopsies in 614 adult patients with Ph1+ chronic myeloid leukemia (CML) to compare histological features with clinical findings. For identification of megakaryopoiesis we used the monoclonal antibody CD61 and additionally the PAS reaction to determine the subfraction of atypical micromegakaryocytes and precursors. Labelling of erythroid precursors was carried out by a monoclonal antibody directed against glycophorin C. In order to selectively stain macrophages and their activated subset we applied CD68 and the GSA-I lectin. Density of argyrophilic fibers (reticulin plus collagen) was measured following Gomori's silver impregnation method. In accordance with laboratory data morphological variables revealed a comparable amount of congruence in the various groups of CML patients derived from different sources. In about 26% of patients early (reticulin) to advanced (collagen) fibrosis was detectable. Significant correlations were calculated between the extent of myelofibrosis with splenomegaly, anemia and increasing numbers of erythroblasts and myeloblasts in the peripheral blood count. These features were assumed to indicate more advanced stages of the disease process with ensuing transition into myeloid metaplasia and consequently were associated with an unfavorable prognosis. Significant relationships were revealed between the number of CD61+ megakaryocytes and more important, also their precursor fraction with the degree of fibrosis. This result extends previous experimental findings regarding the impact of immature elements of this cell lineage for the generation of myelofibrosis. The significant association of erythroid precursors with the number of mature (resident) macrophages including their activated GSA-I subset may shed some light on their functional involvement in iron turnover and hemoglobin synthesis. A modified histological classification of predominant bone marrow features is introduced. This simplified synthesis staging system (Cologne Classification) is not only associated with certain sets of laboratory data, but also with different survival patterns.
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PMID:Bone marrow features and clinical findings in chronic myeloid leukemia--a comparative, multicenter, immunohistological and morphometric study on 614 patients. 1067 1