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)

The immunophenotype (a), ultrastructural features (b) and cell kinetics (c) of circulating megakaryoblasts have been studied in two cases of pure megakaryoblastic and one case of mixed (myeloblastic, megakaryoblastic) cell proliferation in chronic myeloid leukaemia (CML). (a) The blast cells showed early megakaryocyte differentiation antigen (HLA-DR), platelet specific GpIIIa (CD61) and GpIIb-IIIa (CD41) antigens in different percentages. (b) The megakaryoblasts were recognized by the presence of platelet GpIIIa (CD61) demonstrated by an immunoelectron microscopic method. The labelled cells were "lymphocyte-like" megakaryoblasts and cells with features of cytoplasmic maturation (demarcation membranes, alpha granules and vacuoles). (c) Cellular DNA content of the megakaryoblasts was measured by propidium iodide (PI) staining of cells expressing platelet GpIIIa (CD61). Flow cytometric (FC) DNA analysis revealed no aneuploidy and high ploidy (greater than 4N) cell population. In the two cases of pure megakaryoblastic proliferation a high percentage of the megakaryoblasts were in the S-phase, while the non-megakaryoblastic cell fraction showed no elevated S-phase compartment. It is concluded that in CML the circulating megakaryoblasts (1) have a nuclear maturation arrest and accumulation at the level of tetraploid DNA content, (2) surface antigen expression and cytoplasmic organelles show a tendency to mature and (3) in pure megakaryoblastic proliferation the myeloid cells are not in the cell compartment showing high proliferation.
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PMID:Morphologic and flow cytometric analysis of circulating megakaryoblasts in chronic myeloid leukaemia. 192 49

A 46-year-old man was diagnosed as having chronic myelogenous leukemia (CML) in chronic phase in Dec. 1985. In Dec. 1987, anemia and leukocytopenia progressed, and the percentage of blast cells increased in the bone marrow. The blast cells were lymphoblastoid and positive for TdT. It was treated as a lymphoid crisis with vincristine and prednisolone, and complete remission was achieved. However, the blasts (11%) were observed in the bone marrow in Mar. 1988, and the chromosomal analysis revealed 46, XY, t (2q-; 11q+), t (9q+; 22q-) in 13 out of 20 cells. In June, the percentage of the blasts increased again, but chromosomal analysis showed a different karyotype, 46, XY, t(2p-; 11p+), t(9q+; 22q-) which was observed in 9 out of 10 cells. Then, myeloblastoid cells increased rapidly in spite of the chemotherapy in Dec. 1988. The chromosomal analysis showed 46, XY, 2p-, 7q-, 9q+, 11p+, 22q- in all analyzed cells. The rearrangement of the bcr gene could be detected by the Southern blotting. The blasts were positive for CD7, CD11, CD13, CD33, CD36, CD41 and CD42, suggesting that the blasts had the surface phenotypes of both myeloid and megakaryocytoid-lineage. This is a case with the mixed blast crisis that changed from the lymphoid to the myelo-megakaryocytoid in nature, in which three clonal evolutions were observed during the clinical course.
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PMID:[Mixed blast crisis with the cytogenetic evidence of three clonal evolutions]. 236 40

Identification of megakaryocyte precursors with immunohistochemical methods in bone marrow trephine biopsy specimens (embedded in a plastic resin, Immuno-Bed) was performed from patients with blastic phase of chronic granulocytic leukaemia (five cases), from chronic megakaryocytic-granulocytic myelosis (four cases) and from acute megakaryoblastic leukaemia (11 cases). In megakaryoblasts of bone marrow biopsies immunohistochemical reactions using the ABC method and monoclonal antibodies against von Willebrand antigen and GpIIb/IIIa (CD41) were visible in various percentages depending on the maturation's degree of megakaryocyte precursors. The number of circulating blast cells determined by flow cytophotometry was nearly similar to those of observed in biopsies. The greatest bone marrow reticulin content could be detected in acute megakaryoblastic leukaemia cases. Despite the different clinicopathological entities, the presence of the same phenotype (megakaryoblasts) was associated with a short survival in these haematological malignancies (in CGL MKB phase 4.0, in CMGM MKB phase 4.2, and in AML M7 5.8 months, respectively).
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PMID:Megakaryocyte markers in myeloproliferative disorders. 750 75

A novel cell line (KH88) was established from a patient with chronic myelogenous leukemia in blastic crisis. The leukemic blasts had the features of undifferentiated blasts with basophilic agranular cytoplasm and they were focally positive for acid phosphatase and alpha-naphthyl acetate esterase. CD36, CD33, HLADR, and CD71 were expressed on the surfaces of the blast cells. Most blasts were positive for platelet peroxidase activity, and some of them had granules containing aggregates of ferritin molecules. These findings were compatible with those of 'early' erythroblastic leukemia, this established cell line (KH88) having similar characteristics, and actually producing hemoglobin A and hemoglobin F. Although the KH88 cells were negative for megakaryocytic markers, they were induced to express CD41 by phorbol ester. Further, a few KH88 cells were positive for myeloperoxidase. This cell line was thus revealed to have the capacity to differentiate into three lineages, providing a useful model for studying the differentiation of multipotential stem cells. Moreover, a subline of KH88 had a peculiar chromosome abnormality, del(3)(q21q25); it would be useful to study the significance of this chromosomal abnormality.
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PMID:Establishment of a new cell line with the characteristics of a multipotential progenitor from a patient with chronic myelogenous leukemia in early erythroblastic crisis. 828 84

A patient is described with chronic myelogenous leukemia in blastic crisis, in whom numerous circulating platelet fragments and megakaryocytic nuclei were present, with 50% blasts and 50% micromegakaryocytes in the marrow. The blasts expressed myeloid-associated antigens CD34, CD33, and CD13, whereas the micromegakaryocytes were positive for CD41, CD42b, and CD61. These findings suggested a myeloblastic transformation with a possible megakaryoblastic component. Cytogenetic analysis showed rearrangement of 3q26 in the form of t(2;3) (p13;q26), in addition to t(9;22) (q34;q11). Dual-color flow cytometric analysis of DNA content of CD42b-positive cells showed that the micromegakaryocytes were predominantly 2N, indicating a maturation block before nuclear endoreplication and polyploidization. These findings confirmed a combined myeloblastic and megakaryoblastic transformation. It is concluded that dual-color flow cytometric DNA analysis is a useful method for the investigation of abnormal megakaryocytopoiesis in hematologic malignancies.
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PMID:Dual-color flow cytometric analysis of megakaryocytic DNA ploidy in the investigation of blastic phase chronic myelogenous leukemia with rearrangement of 3q26. 850 54

Thirty-four patients with chronic myeloid leukemia in blast crisis (CML-BC) were evaluated for lineage differentiation with immunological markers and the presence of ultrastructural peroxidase. Eighteen (52.9%) were found to have myeloid blast crisis. Cytochemically, myeloperoxidase (MPO) could be detected only in six patients on light microscopy while in the remaining 12 patients, myeloid differentiation was confirmed only by demonstration of MPO either at ultrastructural level or by the reactivity with anti myeloperoxidase (anti MPO) antibody. Six (17.6%) had lymphoid blast crisis as identified by lymphoid specific markers (CD19; CD10; CD7; CD4) along with the absence of myeloid markers. Heterogenous blast cell populations with mixed lineage differentiation were seen in 4 (11.7%) patients. These cases showed both lymphoid (CD19, CD10) and myeloid (anti MPO and ultrastructural MPO) characteristics. A single case of megakaryoblastic blast crisis was identified with positivity for CD41 and CD42 along with the presence of platelet peroxidase at the ultrastructural level. Five cases (14%) of CML blast crisis remained unclassifiable. These results suggest that blast crisis in CML show an arrest of differentiation at an early stage when compared to de novo acute leukemias. This is particularly evident from the fact that MPO could only be demonstrated ultrastructurally or with anti MPO antibody in the majority of patients with myeloid differentiation. It is expected that utilisation of molecular studies including immunoglobulin and T-cell receptor gene rearrangement and m-RNA expression for myeloperoxidase will provide a better insight into the level of differentiation for the presently unclassifiable cases of CML-blast crisis.
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PMID:Immunophenotype and ultrastructural studies in blast crisis of chronic myeloid leukemia. 853 24

Thrombopoietin stimulated blast colony formation in 11/20 acute myelogenous leukaemia (AML) patients studied. The FAB subtypes of the blasts responding to thrombopoietin were not restricted to those of the megakaryocyte lineage, but also included M1-M5 AML blasts. The morphology of colony cells produced by megakaryocytic blasts showed megakaryocytoid features, whereas colony cells produced by M1-M5 AML blasts remained myeloblasts. An increase in CD41 was observed in the cells of colonies produced by blasts from the megakaryocyte lineage involving leukaemia and chronic myeloid leukaemia in blastic crisis. Thrombopoietin receptor was observed on leukaemic blasts which formed colonies following incubation with thrombopoietin.
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PMID:Growth stimulatory effect of thrombopoietin on the blast cells of acute myelogenous leukaemia. 879 Jan 52

We describe very uncommon phenotypic and cytogenetic findings in a 40-year-old female with blast phase of Philadelphia chromosome (Ph)-positive CML. In addition to the t(9;22)(q34;q11) that was detected in all metaphases, a t(11;17)(q23;q21) was identified in 15 of 20 metaphases. Reverse transcription-polymerase chain reaction showed the major and minor bcr/abl fusion transcripts in the cells from a bone marrow (BM) sample. Fluorescence in situ hybridization (FISH) analysis also showed that fusion signals of the bcr and abl probes were found in 95% of blastic cells and in 64% of neutrophils. MLL gene rearrangement was also detected in some blastic cells but not in neutrophils by FISH analysis. Phenotypically, blastic cells expressed mixed lineage antigens such as CD34, CD33, CD13, CD19, CD7, and CD41. Immunogenotypically, some population of BM cells showed monoclonal rearrangements of immunoglobulin heavy chain and T-cell receptor gamma chain genes by Southern blot analysis. Clinical course was aggressive, and therapy was poorly tolerated. Such findings seem to support an association between Ph and an abnormality of 11q23 with poor prognosis, and suggest that the expression of both abnormal genes may be related to this mixed lineage antigen-expressing leukemia.
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PMID:Additional t(11;17)(q23;q21) in a patient with Philadelphia-positive mixed lineage antigen-expressing leukemia. 1134 72

In the blast crisis phase of chronic myelogenous leukemia (CML), Bcr-Abl(+) myeloblasts fail to undergo terminal maturation. The extracellular signal-regulated kinase (Erk) mitogen-activated protein (MAP) kinase has been shown to mediate terminal differentiation of myeloid cells. Interestingly, Bcr-Abl(+) CML cell lines established from blast crisis were found to have low Erk MAP kinase activity. In this study, we analyzed the role of the Gab2 docking protein in regulation of the Erk MAP kinase in Bcr-Abl(+) K562 human CML cells. Overexpression of Gab2 in K562 cells resulted in transcriptional activation of the c-fos serum response element (SRE) promoter, whereas overexpression of SHP2, Grb2, and CrkL had no effect. Activation of the c-fos SRE transcriptional activity by Gab2 required tyrosine 604, which is a SHP2 docking site on Gab2, and the SHP2 tyrosine phosphatase activity. Elk1, c-Jun, and CHOP trans-reporting assays indicated that overexpression of Gab2 selectively activated the Erk2-Elk1 signaling pathway. To determine cellular consequences of elevating the Gab2 level in K562 cells, stable cell lines for doxycycline-inducible expression of the wild-type Gab2 (Gab2WT) and an SHP2-binding defective Gab2 (Gab2Tyr604Phe) were established. Analysis of these cell lines indicated that induction of Gab2WT expression, but not Gab2Tyr604Phe expression, led to Erk activation, growth arrest, cell spreading, and enlargement; expression of megakaryocyte/platelet lineage-specific integrins alphaIIb/beta3 (CD41/CD61); and upregulation of RNA for megakaryocyte/platelet proteins. All of these changes are characteristics of megakaryocytic differentiation. Together, these results reveal Gab2 as a limiting signaling component for Erk MAP kinase activation and terminal differentiation of K562 CML cells.
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PMID:Regulation of the Erk2-Elk1 signaling pathway and megakaryocytic differentiation of Bcr-Abl(+) K562 leukemic cells by Gab2. 1183 Apr 91

A 64-yr-old Japanese man presented with mild anemia, leukocytosis, and thrombocytosis in November 1999. A diagnosis of chronic myeloid leukemia was made with a positive Ph chromosome, and interferon alpha treatment was started, 6 million units a day. Two years later, in October 2001, the patient developed leukocytosis, an increased LDH level, and large blasts with basophilic cytoplasm with cytoplasmic projections appeared in the peripheral blood. Bone marrow aspiration revealed increased blasts (59.6%). These blasts were negative on peroxidase stain, positive on acid phosphatase, and weakly positive on alpha naphthyl butyrate esterase stain and periodic acid-Schiff stain. Immunohistochemical staining with monoclonal antibodies revealed that these blasts were strongly positive with anti-CD41 (glycoprotein IIb/IIIa), weakly positive with CD7, CD33, and CD34, and negative with other monoclonal antibodies. A diagnosis of megakaryoblastic transformation from chronic myeloid leukemia was therefore made. Two-color fluorescence in situ hybridization (FISH) for portions of the major-bcr and abl genes from bone marrow cells revealed two fused signals in 90.6% and one fused signal in 5.8% of 106 cells. A cytogenetic study revealed that bone marrow cells were 69, XYY, +6, -7, +8, -9, t(9;22)(q34;q11), +11, +13, -15, -16, dic(17;18)(p11;p11), -18, +19, +21, der(22)t(9;22) in six of nine examined cells. These findings confirmed that these megakaryoblasts originated from megakaryocytes of the chronic myeloid leukemia clone.
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PMID:Double Ph-positive megakaryoblastic transformation of chronic myeloid leukemia. 1236 19


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