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 order to determine the relationship between the anomalies affecting two types of blood cell in myeloproliferative disorders (MPD), a functional study was performed in individuals presenting with such diseases. Thus, platelet function was investigated by means of Ivy's method for bleeding time, platelet retention to glass beads, aggregation with epinephrine and density distribution on a discontinuous sucrose gradient. Simultaneously, three granulocyte functions, i.e. capillary tube random migration, particle ingestion activity and nitroblue tetrazolium dye reduction were studied. This investigation was carried out in 47 patients presenting with chronic myeloproliferative disorders (MPD): chronic granulocytic leukemia (18 cases), polycythemia vera (18 cases), myelofibrosis (6 cases) and essential thrombocythemia (5 cases). The results of the present study indicate that functional abnormalities are more frequent and more strongly marked in platelets than in phagocytes. The tests most affected were platelet density distribution and granulocytic random migration. Simultaneous assessment of platelet and phagocytic functions, though insufficient in itself to determine the type of MPD or to appraise the prognosis of the disease, could be useful in the diagnosis of some atypical cases of myeloproliferative disorders.
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PMID:Simultaneous study of platelets and phagocytes in myeloproliferative disorders. 659 27

The phagocytic function was investigated by means of four tests (capillary tube random migration, phagocytosis of yeast particles, quantitative nitroblue tetrazolium dye reduction and whole-blood bactericidal activity for Staphylococcus aureus) in 57 patients who had myeloproliferative disorders: 24 had chronic granulocytic leukemia, 22 had polycythemia vera, six had myelofibrosis, and five had essential thrombocythemia. This study confirms the previously reported functional anomalies of phagocytosis in all the myeloproliferative disorders and shows that, despite these anomalies, the increased number of phagocytes allows an efficient whole-blood bactericidal activity, essential for the nonspecific host defence mechanisms.
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PMID:Phagocytosis in myeloproliferative disorders. 693 75

In 1,083 core biopsies of the bone marrow with myeloproliferative diseases 454 cases or 42% were found to have neoplastic megakaryopoiesis. Neoplasia of megakaryocytes was assumed from the conspicuous cytological atypicality revealed by light microscopy, extending and confirming earlier ultrastructural findings. Histopathology of the bone marrow in these patients was described as chronic megakaryocytic-granulocytic myelosis - CMGM - since neutrophilic granulopoiesis is also apparently neoplastic and both cell lineages showed a complete differentiation to mature forms. CMGM should be separated from the chronic granulocytic leukemia - CGL - which consists of only a single line proliferation. The incidence of CGL in our total of 1,083 patients was 25%. Both entities are included in chronic myeloid leukemia - CML - because of the demonstration of the Philadelphia chromosome in the hematopoietic cells of these two groups of patients. Primary or idiopathic thrombocythemia has to be differentiated from CMGM since there is no evidence for malignancy of the granulocytic series.
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PMID:Chronic megakaryocytic granulocytic myelosis-CMGM. A subtype of chronic myeloid leukemia. 693 64

Bone marrow and peripheral blood samples of patients affected by hematologic disorders involving the megakaryocytic line were examined at the electron microscope. While in idiopathic thrombocytopenic purpura the megakaryocytes appeared almost normal, in primary thrombocythemia there were various ultrastructural alterations interpreted as a counterpart of ineffective thrombocytopoiesis. In one patient with blastic chronic myeloid leukemia and in another with acute megakaryoblastic leukemia, the electron microscope study was very useful in the identification of immature megakaryocytes. In fact, analysis of various ultrastructural parameters allowed some blast cells to be attributed to the megakaryocytic series. Furthermore, platelet demarcation system abnormalities and alterations of the circulating thrombocytes confirm the hypothesis that there is a block in megakaryocytic maturation.
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PMID:Ultrastructural alterations of megakaryocytes in some hematologic disorders. 694 59

Blood coagulation and fibrinolysis were studied in 65 patients with chronic myeloproliferative disorders (MPD). They consisted of 28 patients with chronic granulocytic leukemia (CGL) in chronic phase, 7 with CGL in blast crisis, 9 with polycythemia vera (PV), 13 with primary thrombocythemia (PTh) and 8 with primary myelofibrosis (MF). Hemorrhagic and thrombotic complications were observed in 19 and 8 patients, respectively. Activated partial thromboplastin time and prothrombin time were prolonged in many patients. Low factor II levels were observed in some CGL patients. Factor V was decreased in CGL patients in chronic phase and in PV patients. Fibrinogen was either normal or increased in most patients, but an elevation of fibrin/fibrinogen degradation products (FDP) was found in some patients. The VIIIR: Ag/VIII:C ratio was increased in CGL patients in blast crisis, in PV patients and in PTh patients. Antithrombin III and plasminogen were below normal in some patients. Most patients showed a decrease in alpha 2-plasmin inhibitor. These findings suggest that blood coagulation and fibrinolysis are involved in the pathogenesis of the thrombotic and hemorrhagic complications in these patients. Chronic low-grade intravascular coagulation might be present in some patients with MPD.
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PMID:Profile of blood coagulation and fibrinolysis in chronic myeloproliferative disorders. 695 82

Fifty-two patients with chronic myeloproliferative disorders (13 with polycythemia vera; 23 with primary thrombocythemia; 6 with myelofibrosis and 10 with chronic granulocytic leukemia) had low platelet levels of adenine nucleotides and serotonin and abnormal uptake and storage of the amine. The storage pool deficiency was confined to the substances contained in the platelet dense bodies, because alpha-granule and lysosome markers were present in normal amounts. In chronic granulocytic leukemia the storage defect was usually less marked but was accompanied by a decreased formation of thromboxane B2 and normal platelet aggregation in response to arachidonic acid. There was no clearcut relationship of these biochemical abnormalities to prolongation of bleeding time or to thrombotic and hemorrhagic symptoms. The defect was still present in 15 patients after treatment had returned the cell counts to the normal range. Normal levels of 5HT and adenine nucleotides were observed in 8 patients whose platelet counts were high after splenectomy for non-hematological reasons. These findings suggest that biochemical abnormalities are related to the presence in the bone marrow of abnormal clones, resulting in the production of defective platelets.
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PMID:Biochemical and metabolic aspects of platelet dysfunction in chronic myeloproliferative disorders. 710 Dec 43

Essential thrombocythemia is characterized by proliferation of hematopoietic tissue predominantly involving megakaryocytes and resulting in marked thrombocytosis. The disorder has some clinical and laboratory features that resemble those seen in the clonal multipotent stem cell disorders chronic myelogenous leukemia, polycythemia vera, and agnogenic myeloid metaplasia. It has been argued that essential thrombocythemia should be classified together with those disorders as a myeloproliferative syndrome. However, without knowledge of the numbers and types of cells that are involved in essential thrombocythemia, this suggestion remains speculative. Three patients with thrombocytosis were studied. The diagnosis of essential thrombocythemia was considered to be firm in two patients and probable in the third one. The X-linked glucose-6-phosphate dehydrogenase locus was used as a cell marker. Whereas both A and B types of glucose-6-phosphate dehydrogenase were found in nonhematopoietic tissues, only a single-enzyme type was found in the granulocytes, red cells, and platelets from each patient. These data indicate that the disorders in these three patients are clonal and involve multipotent stem cells.
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PMID:Evidence that essential thrombocythemia is a clonal disorder with origin in a multipotent stem cell. 729 2

We have previously demonstrated the presence of a reverse transcriptase-like enzyme in retroviral particles from patients with essential thrombocythemia, polycythemia vera, and chronic myelogenous leukemia. It was subsequently shown that the human genome contains 50 copies of HERV-K. HERV-K is a human endogenous class I retroviral element that contains gag, pol, and env open reading frames. Using both reverse transcriptase-polymerase chain reaction and ribonuclease protection assays, it is demonstrated that the HERV-K pol is expressed in human blood leukocytes. The data indicates that this expression is restricted in CML white cells and is the result of gene regulation.
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PMID:Expression of human endogenous retrovirus (HERV-K) in chronic myeloid leukemia. 750 41

The c-kit proto-oncogene is the receptor gene for the stem cell growth factor. Little is known about the distribution and role of this gene product in malignant hematopoiesis. We analysed here the expression of c-kit in myeloproliferative disorders (MPDs), including chronic myelogenous leukemia (CML), essential thrombocythemia (ET), polycythemia vera (PV), and idiopathic myelofibrosis (IMF) and in the myelodysplastic syndromes (MDS). The c-kit expression of peripheral blood mononuclear cells was measured both at the messenger RNA level using Northern analysis, the RNA dot blot technique with densitometric quantification, the sensitive reverse transcription polymerase chain reaction, and at the protein level using immunofluorescence with monoclonal antibodies. There was a statistically significant increase in c-kit messenger levels in CML, ET, PV, IMF, and MDS as compared with controls (healthy volunteers). The percentage of c-kit protein expressing cells was also higher than in the controls in these disorders. There was a significant correlation of the c-kit protein expression with the CD34 antigen of the cells. Expression correlated with the phase of the disease, being highest in the blast crisis of CML and in the RAEB/RAEBt phases of MDS. The data suggest that increased amounts of circulating stem/progenitor cells with c-kit receptor are found in MPDs and MDS. It is possible that elevated c-kit expression could maintain the affected clone in MPDs and MDS.
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PMID:Expression of the c-kit proto-oncogene in myeloproliferative disorders and myelodysplastic syndromes. 751 74

We evaluated the effects of transforming growth factor-beta 1 (TGF-beta 1) on the growth of hematopoietic progenitors in normal donors and in patients with hematologic malignancies now designed as clonal disorders of multipotential stem cells. TGF-beta 1 at 80 pM exhibited differential effects on the normal hematopoietic progenitors when cells were stimulated with different growth factors, such as G-CSF, GM-CSF, interleukin-3 (IL-3), or stem cell factor (SCF). The suppressive effect by TGF-beta 1 was increased for growth with GM-CSF, IL-3, and SCF, and growth with G-CSF was unaffected in hematologic malignancies, TGF-beta 1 suppression for growth with G-CSF was increased for essential thrombocythemia (ET) and polycythemia vera; chronic myelogenous leukemia (CML) in chronic phase; CML in accelerated phase; CML in myeloid crisis; myelodysplastic syndrome (MDS) in refractory anemia; MDS in refractory anemia with an excess of blasts; and acute myeloblastic leukemia (AML). In CML-myeloid crisis and AML, TGF-beta 1 almost completely abolished the growth, with some patient-to-patient variation. The mean ED50s for the growth of leukemic blast progenitors were 1.6, 1.2, 0.7, and 0.2 pM in the presence of G-CSF, GM-CSF, IL-3, and SCF, respectively, c-myc and c-myb antisense oligonucleotides significantly suppressed the growth of leukemic blast progenitors, but not that of clonogenic cells from normal donors and patients with ET. We also demonstrated that TGF-beta 1 inhibits mRNA expression by AML blasts for c-myc and/or c-myb. When the data are taken together, growth suppression by TGF-beta 1 appears to increase with the progression of clonal evolution in hematologic malignancies.
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PMID:Differential effects of TGF-beta 1 on normal and leukemic human hematopoietic cell proliferation. 754 18


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