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)

Morphometric evaluation was performed on semi-thin sections of core biopsies of the bone marrow and included 20 cases of each group of diseases besides control specimens. (i) Hyperergic myelitis of rheumatic origin. (ii) Chronic granulocytic leukaemia (CGL). (iii) Polycythaemia vera (P. vera). (iv) Chronic megakaryocytic-granulocytic myelosis (CMGM). (v) Myelofibrosis or osteomyelosclerosis (MF/OMS). The following classification of megakaryopoiesis was applied: normal megakaryocytes; giant forms; microforms; intussusceptions; cytoplasmic fragments; naked nuclei. The density distribution shows an increase of megakaryocyte number in those 5 different marrow disorders, ranging from about 13/mm2 in the normal sample up to 65 cells/mm2 in MF/OMS. Microforms are most frequently encountered in CGL, whereas giant megakaryocytes, intussusceptions and many cytoplasmic fragments characterize P. vera, CMGM and MF/OMS. Our measurements suggests 3 distinct categories of bone marrow lesions with corresponding alterations of the megakaryopoiesis: (i) myelitis and CGL; (ii) P. vera; (iii) CMGM and MF/OMS.
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PMID:Density distribution and size of megakaryocytes in inflammatory reactions of the bone marrow (myelitis) and chronic myeloproliferative diseases. 657 91

Morphometry was employed on different entities of chronic myeloproliferative diseases (CMPD) and reactive lesions in addition to normal control specimens. The entities studied included: (1) inflammatory reactions of the bone marrow (so-called myelitis in chronic rheumatoid arthritis), (2) chronic granulocytic leukemia (CGL), (3) agnogenic myeloid metaplasia in an early hypercellular stage (so-called chronic megakaryocytic-granulocytic myelosis, CMGM), (4) agnogenic myeloid metaplasia in an advanced fibrosclerotic stage or osteomyelofibrosis/sclerosis (MF/OMS), (5) polycythemia vera (P. vera), (6) reactive thrombocytosis (TH, as a sequel of miscellaneous conditions) and (7) primary (idiopathic, essential) thrombocythemia (PTH). Evaluation was done on plastic-embedded semithin sections with a constant thickness of 3 micron in approximately 20 cases of each group of CMPD. The following parameters were determined: (1) density distributions of the megakaryocyte and non-megakaryocyte compartments, (2) arrangement of megakaryopoiesis in the bone marrow space (i.e., inhomogeneity or clustering) and (3) the fine structure of megakaryocytes in PTH, with a quantitative analysis of the nuclear morphology by circular deviation and contour factors. The megakaryocyte morphology was closely related to a facultative or obligatory increase of the platelet count in these various entities of CMPD and was separable into two major categories: (1) controls, CGL and myelitis versus (2) CMGM, MF/OMS, P. vera, TH and PTH. These two categories were distinguishable by the prominence of megakaryopoiesis in the bone marrow as well as the elevated platelet counts in the periphery. Moreover, in comparison with CMGM and MF/OMS, PTH was characterized by an apparently normal maturation and a conspicuous polyploidization of megakaryocytes according to the nuclear morphology, which was similar to that of P. vera. Our results suggest that PTH presents a monolinear growth of the megakaryopoiesis in the same way as CGL exhibits a monolinear proliferation of the neutrophilic granulopoiesis. This is in contrast to the mixed cellularity of both the megakaryocyte and granulocyte lineage in CMGM and MF/OMS.
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PMID:Megakaryopoiesis in chronic myeloproliferative diseases. A morphometric evaluation with special emphasis on primary thrombocythemia. 659 64

Leukaemic cells from a patient in the blast crisis of chronic myeloid leukaemia were subjected to a surface marker analysis using a panel of monoclonal antibodies recognizing differentiation antigens of myeloid (MY7, MY906, VIM D5, M phi P9), erythroid (VIE G4), megakaryocyte (AN51), T-lymphoid (WT1, 10.2, OKT3, OKT4, OKT6, OKT8, OKT11A) and B-lymphoid cells (B1, B2, Y29/55), common ALL-antigen (VILA1), non-lineage-restricted antigens (OKT9, OKT10), monomorphic HLA-DR determinants (7.2) as well as TdT. When the patient entered his first blast crisis, his blasts expressed a phenotype corresponding to an immature myeloid cell (7.2+, MY7+, My906+, VIM D5-). Ph1-chromosome-positive blasts from this patient's first relapse had completely changed their surface marker characteristics: they had become TdT-positive and exhibited surface features characteristic of early T blasts (WT1+, 10.2+, OKT9+, OKT10+, 7.2-, OKT6-). Together, these features provide evidence that myeloid cells may share a common precursor with T cells.
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PMID:Ph1 positive blast crisis of chronic myeloid leukaemia exhibiting features characteristic of early T blasts. 660 23

Micromegakaryocytes (MMK) were defined morphologically by the cell area, nucleus form and cytoplasmic structure. Bone marrow smears of 7,156 patients were retrospectively analyzed. MMK were found most frequently and abundantly in acute non-lymphatic leukaemia, chronic myeloid leukaemia and pre-leukaemia. The presence of more than 10% MMK in the megakaryocyte population suggest a pre-leukaemic condition or non-lymphatic leukaemia. The platelet production of MMK is probably quantitatively normal although a functional defect is suspected.
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PMID:Micromegakaryocytes in Human Bone Marrow. 677 70

A 52-year-old man with Ph1-positive chronic myelogenous leukemia (CML) developed a blastic transformation in which the predominant cell type micromegakaryocytes. He did not respond to treatment. A review of the 15 previously reported cases of patients with circulating megakaryocyte abnormalities in association with either CML or a Ph1 chromosome positive myeloproliferative disorder suggests a female predominance rather than the usual male predominance of CML. Survival of the six patients reported as megakaryoblastic transformation of CML as well as this patient was poor.
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PMID:Megakaryoblastic transformation of chronic myelogenous leukemia. 694 25

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

Thirty-five patients with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) were classified on the basis of the fusion pattern of bcr-abl mRNA determined by the reverse-transcriptase-polymerase chain reaction (RT-PCR) method. Semiquantitative assay of the bcr exon 2/abl exon 2 fused mRNA (b2-a2) and bcr exon 3/abl exon 2 fused mRNA (b3-a2) resulted in 21 patients showing b3-a2 type mRNA, seven showing b2-a2 type and seven showing coexpression. Quantification of the autoradiographic signals of amplified products was estimated using an MCID image analysis system. The relative intensity was defined as the ratio of bcr-abl signal to that of beta-actin. The relationship between the semiquantified bcr-abl mRNA and the platelet/megakaryocyte counts was analyzed. A possible correlation was found between the semiquantified b3-a2 type mRNA and the platelet (p < .05, N = 28) and megakaryocyte (p < .05, N = 13) counts of these patients. This finding suggests the possibility that b3-a2 mRNA may affect the thrombopoietic activity in Ph1-positive CML in a dose-response manner.
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PMID:Possible correlation of b3-a2-type bcr-abl messenger RNA defined by semiquantitative RT-PCR to platelet and megakaryocyte counts in Philadelphia-positive chronic myelogenous leukemia. 752 Jul 86

It has been suggested that the breakpoint location within the M-BCR segment of chromosome 22 and the type of chimeric mRNA BCR/ABL (b2a2 or b3a2) are associated with differences in the clinical and hematological characteristics of chronic myelogenous leukemia (CML). To assist in clarifying this matter, in a series of Ph-positive CML patients the relationship of both the breakpoint location within M-BCR (n = 71) and the type of chimeric mRNA BCR/ABL (n = 40) with the chronic phase duration, patients' survival, and thrombopoietic activity was analyzed. Median survival for patients with breakpoints in zones 1+2+3 (n = 38) and zones 4+5 (n = 31) was 62 and 75 months, respectively, the difference being not significant; patients with breaks in zones 1+2 (n = 19) and zones 3+4+5 (n = 50) had a median survival of 50 and 67 months, respectively (P also not significant). Moreover, no significant differences were found in the survival of patients with b2a2 (n = 16) and b3a2 (n = 24) mRNA junctions. Finally, no differences were observed in the platelet or megakaryocyte counts between patients with breakpoints in extremes 5' and 3' nor between patients with b2a2 and b3a2 mRNA. The above results are in agreement with those reported in most recent studies, confirming the lack of clinical relevance of molecular pattern in CML.
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PMID:Analysis of the clinical relevance of the breakpoint location within M-BCR and the type of chimeric mRNA in chronic myelogenous leukemia. 759 78

The BCR/ABL oncogenic tyrosine kinase is responsible for initiating and maintaining the leukemic phenotype of Philadelphia chromosome (Ph1)-positive cells. Phosphatidylinositol-3 (PI-3) kinase is known to interact with and be activated by receptor and nonreceptor tyrosine kinases. We investigated whether PI-3 kinase associates with and/or is regulated by BCR/ABL, whether this interaction is functionally significant for Ph1 cell proliferation, and, if so, whether inhibition of PI-3 kinase activity can be exploited to eliminate Ph1-positive cells from bone marrow. We show that the p85 alpha subunit of PI-3 kinase associates with BCR/ABL and that transient expression of BCR/ABL in fibroblasts and down-regulation of BCR/ABL expression using antisense oligodeoxynucleotides (ODNs) in Ph1 cells activates and inhibits, respectively, PI-3 kinase enzymatic activity. The use of specific ODNs or antisense constructs to downregulate p85 alpha expression showed a requirement for p85 alpha subunit in the proliferation of BCR/ABL-dependent cell lines and chronic myelogenous leukemia (CML) primary cells. Similarly, wortmannin, a specific inhibitor of the enzymatic activity of the p110 subunit of PI-3 kinase, inhibited growth of these cells. The growth of normal bone marrow and erythromyeloid, but not megakaryocyte, progenitors was inhibited by p85 alpha antisense [S]ODNs, but wortmannin, at the concentrations tested, did not affect normal hematopoiesis. The proliferation of two BCR/ABL- and growth factor-independent cell lines was not affected by downregulation of the expression of the p85 alpha subunit or inhibition of p110 enzymatic activity, confirming the specificity of the observed effects on Ph1 cells. Thus, PI-3 kinase is one of the downstream effectors of BCR/ABL tyrosine kinase in CML cells. Moreover, reverse transcriptase-polymerase chain reaction performed on single colonies to detect BCR-ABL transcripts showed that wortmannin was able to eliminate selectively CML-blast crisis cells from a mixture of normal bone marrow and Ph1 cells.
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PMID:Phosphatidylinositol-3 kinase activity is regulated by BCR/ABL and is required for the growth of Philadelphia chromosome-positive cells. 760 2

The incorporation of other marrow cells into megakaryocytes, termed emperipolesis, has been studied in paraffin biopsy sections from 17 untreated patients with myeloproliferative disorders (MPDs). The group consisted of 12 females and 5 males, aged from 34 to 72 years (mean 51.3). Patients with essential thrombocythemia (ET)--9, chronic granulocytic leukemia (CGL)--4, polycythemia vera (PV)--3, and myelofibrosis (MF)--1 were included into the study. Clusters of large polyploid megakaryocytes were observed in anatomic relation to the marrow sinusoidal system. Emperipolesis has been scored as being present or absent per 100 megakaryocytes/slide. Cells found within megakaryocytes were mostly erythroblasts and mature granulocytes. The number of incorporated cells varied from 1 to 7 per one megakaryocyte. Considering the 17 patients with MPDs, emperipolesis was observed in a vast majority of those with ET(8/9) and PV(2/3), in some with CGL(1/4), but not in MF. The mechanism of megakaryocytic emperipolesis remains unclear. Adhesion molecules on megakaryocytes and incorporated cells may possible mediate the cell-to-cell interactions important for emperipolesis.
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PMID:[Emperipolesis in megakaryocytes in patients with thrombocytosis in the course of myeloproliferative disorders]. 765 23


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