Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 57-year-old woman visited to our hospital complaining of paresthesia in the right leg. She had no abnormal physical findings. However, the peripheral blood examination demonstrated 7% basophilia with 8000/microliters WBC count and decreased neutrophil alkaline phosphatase activity (score 37, rate 19%). She was diagnosed as Ph1 chromosome positive CML in early phase by the chromosomal analysis of bone marrow cells. She received subcutaneous injection of natural interferon-alpha at a dosage of 600 x 10(4) IU daily from March 10, 1987. The dosage and administration interval were gradually reduced and prolonged. Since November 1988, weekly injections of 300 x 10(4) IU has been administered as maintenance therapy. Cytogenetic improvement was seen at 4 months after the start of IFN. Disappearance of Ph1 chromosome positive cells was observed on December 11, 1987. It was suggested that the administration of IFN from the early chronic phase played an important role in the control of the disease.
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PMID:[Natural interferon-alpha induced cytogenetic complete remission in a patient with chronic myelocytic leukemia, diagnosed in early chronic phase with basophilia and normal blood cell counts]. 163 74

The hepatic abnormalities that developed after the splenectomy in 10 subjects with idiopathic myelofibrosis were analyzed. In all patients in whom a liver biopsy was performed during the splenectomy, extramedullary hematopoiesis was demonstrated, consisting of dysmorphic megakaryocytes primarily localized in the sinusoids, often accompanied by erythroid precursors. Following splenectomy, a significant increase in both the liver size and serum levels of alkaline phosphatase, bilirubin or gamma-glutamyl transpeptidase was found within 6 months, whereas no such increase was observed in the serum aspartate transaminase and alanine transaminase concentrations. In addition, 2 patients developed acute liver failure leading to death at 3 and 4 weeks from splenectomy, respectively. In contrast with these findings, no hepatic alterations were observed in 10 chronic myeloid leukemia patients who were also submitted to splenectomy.
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PMID:Liver dysfunction following splenectomy in idiopathic myelofibrosis: a study of 10 patients. 167 28

A morphometric analysis of bone marrow biopsy specimens from patients with myelofibrosis was made to determine the amount of lattice fiber and the number of megakaryocytes, to compare the degree of myelofibrosis in primary and secondary myelofibrosis, and to assess the relationship between the morphometric findings and other parameters. Eight patients with agnogenic myeloid metaplasia (AMM) and six with chronic myelogenous leukemia associated with frank myelofibrosis (CML-MF) were studied. When the main clinical, hematological, and laboratory features of both groups of patients were compared, the only significant difference was in the neutrophil alkaline phosphatase score. Morphometric study showed that the amount of lattice fiber and the number of megakaryocytes in AMM were not statistically different from those in CML-MF, and that neither the number of megakaryocytes nor the platelet count correlated with the amount of lattice fiber.
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PMID:Morphometric analysis of myelofibrosis in agnogenic myeloid metaplasia and chronic myelogenous leukemia. 168 56

We evaluated the in vitro effects of recombinant human (rh) granulocyte colony-stimulating factor (G-CSF) and rh granulocyte-macrophage CSF (GM-CSF) on neutrophil alkaline phosphatase (NAP) activity and the incorporation of amino acids into polymorphonuclear leukocytes (PMN) from normal individuals and patients with chronic myelogenous leukemia (CML). Both the NAP activity and incorporation of amino acids into PMN were enhanced by the addition of G-CSF in a dose-dependent manner. NAP activity induced by G-CSF in PMN from CML patients showed a greater increase than that in PMN from normal controls. In contrast to G-CSF, GM-CSF did not affect the NAP activity in PMN in spite of the enhanced incorporation of amino acids into PMN by GM-CSF. Interestingly, both the NAP-inducing ability of G-CSF and its enhancing ability for amino acid incorporation were suppressed by GM-CSF in a dose-dependent manner when PMN were incubated with various concentrations of GM-CSF in addition to 100 ng/ml of G-CSF. These observations suggest that G-CSF and GM-CSF act differently: G-CSF induces NAP synthesis in PMN, whereas GM-CSF negatively modulates the effect of G-CSF. Further, it is suggested that protein synthesis induced by G-CSF is negatively modulated by GM-CSF in a general fashion.
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PMID:Granulocyte-macrophage colony-stimulating factor suppresses induction of neutrophil alkaline phosphatase synthesis by granulocyte colony-stimulating factor. 169 Nov 3

The levels of leukocyte alkaline phosphatase (LAP) messenger RNA (mRNA) are evaluated in B and T lymphocytes, monocytes, and polymorphonuclear cells (PMNs), and this transcript is found to be present only in PMNs. Precursors of the myelomonocytic pathway, represented by leukemic cells isolated from several cases of chronic myelogenous leukemia (CML) in its stable and blastic phase and acute myelogenous leukemia (AML), are devoid of LAP transcript. These data support the notion that LAP is a marker of the granulocyte terminal differentiation. Despite the absence of LAP mRNA in both the myeloid and the lymphoid precursors, nuclear run-on experiments show constitutive transcription of the LAP gene in leukemic cells obtained from AML, CML, as well as acute lymphoblastic leukemia (ALL) and B-cell chronic lymphocytic leukemia (B-CLL). In CML and in chronic myelo-monocytic leukemia (CMML) PMNs, granulocyte colony-stimulating factor (G-CSF) specifically accumulates LAP mRNA without showing a substantial increase in the rate of transcription of the LAP gene. Once increased by G-CSF, LAP mRNA is very stable, showing a half-life of more than 4 hours in the presence of actinomycin-D. G-CSF is suggested to play a pivotal role in the modulation of LAP transcript in PMNs.
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PMID:Expression of leukocyte alkaline phosphatase gene in normal and leukemic cells: regulation of the transcript by granulocyte colony-stimulating factor. 170 29

The activity of alkaline phosphatase and peroxidase was measured in polymorphonuclears in 20 cases of myelodysplasia syndromes, 10 cases of chronic myeloid leukaemia. Reduced phosphatase activity was found in 5 cases and peroxidase activity in 3 cases of myelodysplasia syndromes. No evident correlation was noted between the activity of these enzymes and prognosis. Increased proportion of peroxidase-negative granulocytes was observed, moreover, in most cases of chronic myeloid leukaemia. The observations will be continued in larger material.
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PMID:[Results of selected cytochemical studies of mature granulocytes in myelodysplastic syndromes and various other hematologic diseases]. 182 68

Portal hypertension with varices developed in 18/675 patients with chronic myeloid leukaemia (CML) in a randomized trial comparing busulphan with busulphan and thioguanine. All 18 had received the drug combination and none busulphan alone (P less than 0.0001). Ascites was also seen significantly more often in the combination arm (P less than 0.05). These results strongly suggest that the addition of thioguanine was responsible for the development of portal hypertension. The histological features were predominantly those of non-cirrhotic portal hypertension--either idiopathic portal hypertension with minimal morphological abnormalities, nodular regenerative hyperplasia or in two cases leukaemic infiltration only was noted. Cirrhosis was present in 3/16 cases studied. Both treatment groups developed abnormal liver function tests during the chronic phase, but particularly with progression of the disease. During chronic phase abnormalities were significantly more frequent in those receiving busulphan and thioguanine-alkaline phosphatase (P less than 0.02), transaminases (P less than 0.04), bilirubin (P less than 0.05), multiple abnormalities (P less than 0.01). The development of portal hypertension was often associated with abnormalities of these tests; however, lack of specificity precludes their use as a predictor of subsequent clinical problems. Thioguanine confers no survival advantage in this disease. In view of its hepatotoxicity it should not be used routinely for maintenance of control in chronic phase CML.
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PMID:Thioguanine used in maintenance therapy of chronic myeloid leukaemia causes non-cirrhotic portal hypertension. Results from MRC CML. II. Trial comparing busulphan with busulphan and thioguanine. 195 75

The aim of the present study was to evaluate the surface membrane glycoproteins of pseudo-Pelger granulocytes in six patients suffering from chronic myeloid leukaemia (CML). We studied the functional and immunochemical activities of five monoclonal antibodies (MoAb) minimally reactive with integrin familial antigens of pseudo-Pelger granulocytes. The study conducted with cytofluorimetric and immunological alkaline phosphatase anti-alkaline phosphatase (APAAP) analysis showed a decreased expression of CD11b/CD18 detected by antibodies OKM1, 60.1 and 60.3 (P less than 0.001). Lymphocyte function associated antigen (LFA-1) was expressed in normal amounts in pseudo-Pelger granulocytes. There was decreased expression of CD11b/CD18 in pseudo-Pelger granulocytes with respect to controls (P less than 0.001) after stimulation with formyl-met-leu-phe (FMLP). We conclude that acquired pseudo-Pelger granulocyte dysfunction may be correlated to decrease of surface glycoprotein expression of CD11b/CD18.
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PMID:Surface expression of CD11b/CD18 of pseudo-Pelger granulocytes in chronic myeloid leukaemia. 198 28

We report here a patient with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) in chronic phase in whom the alkaline phosphatase activity of neutrophils in the peripheral blood was low while at the same time the alkaline phosphatase content of neutrophils present in the urine was elevated. This observation provides independent clinical support for the recent experimental finding that an extrinsic factor (granulocyte colony-stimulating factor) controls alkaline phosphatase expression in human neutrophils.
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PMID:Neutrophil alkaline phosphatase activity in the urinary neutrophils of a patient with chronic myelogenous leukemia. 198 87

The clinical constellation of leukocytosis, thrombocytosis, and low or absent stainable neutrophil alkaline phosphatase (NAP) is considered characteristic of chronic myelogenous leukemia (CML). CML with eosinophilic differentiation (eosinophilic leukemia) is well described, and leukemia and other clonal hematologic malignancies are associated with the syndrome of eosinophilic fasciitis. We describe leukocytosis, thrombocytosis, eosinophilia, mild basophilia, and absent stainable NAP, initially suggesting the diagnosis of CML in a patient with the eosinophilia myalgia syndrome associated with L-tryptophan use, a condition resembling eosinophilic fasciitis. Cytogenetic and molecular genetic studies failed to demonstrate a clonal proliferation of eosinophils.
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PMID:Absent neutrophil alkaline phosphatase in the eosinophilia myalgia syndrome associated with L-tryptophan use. 201 75


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