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)

An immunohistochemical and morphometric study was performed on routinely processed trephine biopsies of the bone marrow in 30 normal individuals and in 90 patients with various subtypes of chronic myeloproliferative disorder. Using a new monoclonal antibody (PG-M1) directed against a formalin-resistant epitope on macrophages and by employment of the Prussian blue reaction, quantitation of this cell population was feasible. Morphometric analysis revealed that the number of iron-laden macrophages represented only a fraction of the total number of histiocytic reticular cells. As could be expected, in polycythaemia rubra vera, no haemosiderin deposits were detectable, but the content of macrophages slightly exceeded that of the normal bone marrow. In chronic myeloid leukaemia 9 of 30 patients showed a significant increase in PG-M1-positive reticular cell elements. These were consistent with pseudo-Gaucher cells, sea-blue histiocytes and intermediate cell types. Primary (idiopathic) myelofibrosis-osteomyelosclerosis was characterized by a significant increase in macrophages (25 of 30 patients). Involvement of macrophages in the complex mechanisms generating bone marrow fibrosis and angiogenesis and in bone remodelling (osteosclerosis) may be responsible for this finding.
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PMID:Macrophages in normal human bone marrow and in chronic myeloproliferative disorders: an immunohistochemical and morphometric study by a new monoclonal antibody (PG-M1) on trephine biopsies. 163 47

Leukocytosis, mild anemia, thrombocytosis, and panhyperplasia in the marrow characterize the early stages of most of the CMPD, whereas extramedullary hematopoiesis (such as in the spleen or liver), peripheral cytopenias (anemia, leukopenia, or thrombocytopenia), and myelofibrosis, with or without osteosclerosis, reflect the changes seen in the later stages. Transitions among the different CMPD and termination in acute leukemia or marrow failure also are common. CML often is characterized by leukocytosis and the presence of the entire spectrum of granulocytes (mature and immature) in the blood and marrow, reduced LAP, hypercellularity with prominent granulocytic hyperplasia in the marrow, Ph chromosome, and bcr-abl gene rearrangement. Typical features of AMM include leukoerythroblastosis, teardrop poikilocytosis, anemia, increased or normal LAP, prominent megakaryocytic hyperplasia in the marrow, dyshematopoiesis, and hyperplastic or fibrotic/sclerotic marrow.
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PMID:Myeloproliferative disorders. Classification and diagnostic features with special emphasis on chronic myelogenous leukemia and agnogenic myeloid metaplasia. 227 76

Bone marrow biopsies of 850 patients with chronic myeloproliferative disorders were taken at initial diagnosis; and 169 sequential biopsies over periods of one to 188 months. Three micron sections of all biopsies were evaluated semiquantitatively with reference to the proliferating cell lines, anomalies of megakaryocytes, and fibrosis or osteosclerosis. Correlations between initial histological findings, clinical, haematological, and survival data were analysed statistically. The predominant cell lines distinguished the classical entities of polycythaemia vera, primary thrombocythaemia, and chronic myeloid leukaemia and correlated with their different prognoses, while megakaryocytes characterised subgroups that were prone to fibrotic or blastic transformation. Based on the initial histological, clinical, and haematological data analysed a working classification of chronic myeloproliferative disorders was proposed that permits recognition of both typical and atypical cases of chronic myeloproliferative disorders.
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PMID:Working classification of chronic myeloproliferative disorders based on histological, haematological, and clinical findings. 345 24

The neoplastic proliferation of tissue mast cells constitutes a group of rare diseases that have localized and systemic variants. The cytologic (n = 7) and histologic (n = 38) findings in bone marrow from a total of 45 patients with systemic mastocytosis were evaluated. Three distinct histologic patterns of marrow involvement were distinguished. In 21 cases a patchy or focal infiltration pattern was encountered. Mast cell aggregates were located predominantly in peritrabecular and perivascular areas. The adjacent trabeculae were thickened. A dense network of reticulin fibers and foci of lymphocytes accompanied the mast cell infiltrates. Increased numbers of eosinophils frequently demarcated the mast cell infiltrates from the surrounding tissue. In the noninfiltrated marrow areas hematopoiesis and the distribution of fat cells appeared to be normal. This histologic pattern, designated type 1, was observed exclusively in patients showing primary involvement of the skin, indistinguishable from urticaria pigmentosa. In 14 additional cases peritrabecular and perivascular sheets of mast cells, with concomitant fibrosis and osteosclerosis, were also present. Unlike the findings in type 1, however, the noninfiltrated marrow areas showed marked reductions in fat cell content and markedly increased granulocytopoiesis or increased numbers of blast cells (infiltration pattern type 2). On the basis of the hematologic and clinical findings, chronic myeloid leukemia was diagnosed in six of these cases, myelomonocytic leukemia in three cases, and acute myeloid leukemia in two cases. The bone marrow of three patients was diffusely infiltrated by atypical mast cells, leading to marked hypoplasia of fat cells and blood cell precursors. These histologic features were identified as infiltration pattern type 3. The diagnosis of mast cell leukemia was confirmed in all three cases by the presence of numerous mast cells in the blood. The prognosis for patients with the type 1 marrow infiltration pattern and primary skin involvement was favorable (actuarial survival rate five years after diagnosis, 0.75). This variant was called benign systemic mastocytosis. Primary skin involvement did not occur in the patients with type 2 or 3 infiltration patterns. The prognosis for these patients was poor (actuarial survival five years after diagnosis, 0.17 for type 2 and 0.00 for type 3). These two forms were accordingly designated malignant systemic mastocytosis.
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PMID:Bone marrow findings in systemic mastocytosis. 386 Apr 69

An autopsy case of a 50 years old woman who manifested chronic myelocytic leukemia (CML) with secondary myelofibrosis (SMF) is reported. The interesting point of this case was a marked diffuse myelofibrosis (MF) with osteosclerosis, so that it was difficult to make a diagnosis of either CML or idiopathic myelofibrosis (IMF), but both clinical and histological findings supported the diagnosis of CML with SMF. Her long term busulfan therapy was suspected as being the cause of this severe MF. The relationship of CML and IMF was also discussed.
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PMID:Chronic myelocytic leukemia with marked myelofibrosis and osteosclerosis. 657 70

Forty-one patients with chronic myeloid leukemia (CML) were divided into 3 groups: 13 patients in a chronic phase prior to cytostatic treatment group 1; 17 patients in a chronic phase treated with myelosan group 2; 11 patients in a blast transformation phase group 3. All of them underwent abdominal sonography in line with marrow histomorphometry. Ultrasound investigation is thought indispensable in examination of CML patients as it registers negligible enlargement of the liver and spleen and provided their echo structure. It makes possible to trace stages of the tumor process development. CML involves in the pathological process the kidneys as shown by changes in the echo pattern, concrements are often formed in the pelvicalyceal system. Group 1 patients demonstrated reduced area of the bone tissue by morphometrical evaluation of the bone marrow. This means prevalence of osteolysis in CML onset. In group 3 patients this value is higher indicating osteosclerosis predominance. Comparison of the ultrasonic and histomorphometric data suggest that enlargement of the spleen and liver with diffuse vegetations of the connective tissue and their fibrotic lesion of the parenchyma correlated with the severity dissemination of hemopoietic tissue collagen fibrosis. It is evident that CML is characterized by fibrosis involving simultaneously bone marrow, splenic and hepatic parenchyma.
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PMID:[The necessity for the combined use of the ultrasonic study of the abdominal cavity organs and of the histomorphometry of the bone marrow in chronic myeloleukemia]. 821 74

Philadelphia chromosome-positive essential thrombocythaemia (Ph(+)-ET) and chronic granulocytic leukaemia (Ph(+)-CGL) constitute a separate malignant disease entity, whereas essential thrombocythaemia (ET), polycythaemia vera (PV) and chronic megakaryocytic granulocytic metaplasia (CMGM) belong to the Philadelphia chromosome-negative (Ph-) myeloproliferative disorders. The megakaryocytes in Ph(+)-ET and Ph(+)-CGL are abnormal and small with round nuclei, showing little lobulation. Both the number and size of megakaryocytes in Ph-ET, -PV and -CMGM are typically increased. Enlarged megakaryocytes with mature cytoplasm and multilobulated nuclei and their tendency to cluster in a normal or slightly increased cellular bone marrow represent the hallmark of ET. In reactive thrombocytosis the size and morphology of increased megakaryocytes are normal. The characteristic increase and clustering of enlarged mature and pleomorphic megakaryocytes with multilobulated nuclei and proliferation of erythropoiesis in a moderate to marked hypercellular bone marrow with hyperplasia of dilated sinuses is the diagnostic hallmark of untreated PV. In secondary polycythaemia, in which increased cellularity of the erythroid cell line may be present, the number, size and morphology of megakaryocytes remain small and normal. CMGM, including early stages without myelofibrosis and advanced myelofibrotic stages of agnogenic myeloid metaplasia, appears to be a distinct neoplastic proliferation of neutrophilic granulopoiesis and megakaryopoiesis. The histopathology of the bone marrow in CMGM is dominated by atypical, enlarged and immature megakaryocytes with cloud-like nuclei which are not seen in ET and PV. Myelofibrosis in ET, PV and CMGM is graded in no reticulin fibrosis (MFO), early reticulin fibrosis (MF1), advanced reticulin sclerosis with minor collagen fibrosis (MF2) and advanced collagen fibrosis with or without osteosclerosis (MF3). Myelofibrosis is not a feature of ET, may occur in PV, and constitutes a prominent feature of CMGM during the natural history of the disease.
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PMID:Diagnostic criteria of the myeloproliferative disorders (MPD): essential thrombocythaemia, polycythaemia vera and chronic megakaryocytic granulocytic metaplasia. 928 42

The aim of this review is to evaluate morphological characteristics of the different subtypes of chronic myeloproliferative disorders (MPDs) derived by applying immunohistochemical and morphometric techniques to bone marrow biopsies and to combine these results with relevant clinical parameters. In comparison to control specimens, a significant decrease in erythroid precursors is determinable in chronic myeloid leukemia (CML), while this cell lineage is most prominent in polycythemia vera (PV) and moderately to markedly reduced in idiopathic myelofibrosis (IMF). On the other hand, neutrophilic granulopoiesis shows a predominance in CML and a relevant increase in PV, but no conspicuous changes are detectable in essential thrombocythemia (ET). CML is characterized by a prevalent growth of dwarflike micromegakaryocytes, occurring in particular in the so-called megakaryocyte-rich subtypes (about 30%). This finding differs significantly from the pleomorphous aspect, i.e. , clusters of small to giant-sized megakaryocytes in PV and the grossly abnormal (dysplastic) appearance of this cell lineage in patients with IMF. Similar cytological abnormalities of megakaryopoiesis consistent with maturation defects are never encountered in ET. The incidence of mature (resident) macrophages (phagocytic reticular cells) is significantly enhanced in IMF in comparison to the other MPDs and controls. Moreover, there is a striking difference in the density of reticulin-collagen fibers, ranging from normal (ET) to extreme values (IMF). In IMF more than 80% of the patients present with some degree of myelofibrosis-osteosclerosis at diagnosis, while the rest show an initial prefibrotic, hypercellular stage. This feature deserves special attention since, when accompanied by thrombocythemia, it may simulate ET. Sequential bone marrow biopsies in patients with IMF disclose that evolution of myelofibrosis is progressive, but occurs at a variable and unpredictable speed. A synoptical approach regarding clinical diagnosis and histological subtyping of MPDs is explicitly recommended and demonstrated by sets of diagnostic criteria. This rationale requires equal consideration of laboratory data and morphology by clinicians to include well-defined subtypes of MPDs into prospective management studies. Furthermore, it may even warrant follow-up studies and repeated bone marrow examinations in initially unclassifiable cases.
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PMID:Histochemistry and morphometry on bone marrow biopsies in chronic myeloproliferative disorders - aids to diagnosis and classification. 1060 93

In a case with secondary myelofibrosis occurring after essential thrombocythemia, cytogenetic analysis revealed an isolated translocation t(X;17)(q27;q22) in all cells. We found that a bacterial artificial chromosome (BAC) encompassing the breakpoint on chromosome 17 long arm contained only one gene, NOG. We therefore investigated the occurrence of this rare breakpoint in myeloproliferative disorders (MPDs). We identified three more patients with a 17q abnormality in MPDs: myelofibrosis with myeloid metaplasia (MMM); chronic myeloid leukemia positive for t(9;22)(q34;q11) with additional t(4;17)(p15;q22) at diagnosis; and myelofibrosis complicating polycythemia vera. All three cases exhibited a split of BACs containing NOG. The protein encoded by NOG, noggin, acts as an antagonist to bone morphogenetic secreted protein 2 and 4 (BMP2 and BMP4). A comparative analysis of gene expression on Agilent 22K oligonucleotide microarrays in purified CD34+ cells from the blood of MMM patients showed significant downregulation of BMPR2, BMPR1B, BMP2, and BMP8; upregulation of BMP3 and BMP10; and a trend to lower expression of NOG. Thus, given that expression and release of BMPs are important in the induction of osteosclerosis and angiogenic activity, the observed BMP deregulations could be triggered by potential NOG genetic alterations in the four cases here described, and may contribute to the myelofibrotic process characterized by bone marrow stromal reaction including collagen fibrosis, osteosclerosis, and angiogenesis.
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PMID:Bone morphogenetic protein antagonist gene NOG is involved in myeloproliferative disease associated with myelofibrosis. 1788 3