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)

GVH mortality was encountered in each of six parental-F1 hybrid combinations with antigenic disparity sufficient to cause strong positive CML. Mortality was encountered in only one of nine combinations in which CML is negative (or weak). The CML assay may thus be useful, but is not perfect, in prediction of GVH mortality. Of the eight CML-negative, GVH nonlethal combinations, three were MLC positive and also activated donor T-cell proliferation in vivo.
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PMID:Correlation of graft-versus-host mortality and positive CML assay in the mouse. 1 Jun 48

High levels of terminal deoxynucleotidyl transferase have been observed in leukocytes of 7 out of 20 patients with chronic myelogenous leukemia in acute blast phase of the disease. These levels are comparable to the levels observed in human and calf thymus gland and cell lines with some T cell characteristics (Molt 4 and 8402). Negligible levels of this activity were observed in chronic myelogenous leukemia not in an acute blast phase of the disease, chronic lymphocytic leukemia, human B cells, mature T cells, and the mixed population of lymphocytes present in normal human blood. The detection of this enzyme in some patients with chronic myelogenous leukemia in acute blast phase of the disease suggests that the blast proliferation may involve primitive stem cells which have more lymphoid than myelogenous characteristics. This enzyme assay may be of use as a biological marker for following patients during treatment and in remission.
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PMID:Terminal deoxynucleotidyl transferase as a biological marker for human leukemia. 1 27

Extracts of human normal and leukemic leukocytes contain an enzyme that catalyzes a transfer of labeled methyl carbon from N5-[14C]methyltetrahydrofolate to tryptamine. Evidence is presented that this reaction is not attributable to a methyltransferase but to the following reaction sequence: (a) an oxidation of N5-[14C]methyltetrahydrofolate to N5, N10-[14C]methylenetetrahydrofolate that is catalyzed by N5, N10-methylenetetrahydrofolate reductase (EC 1.1.1.68); (b) spontaneous release of [14C]formaldehyde from N5, N10-[14C]methylenetetrahydrofolate; and (c) nonenzymatic condensation of [14C]formaldehyde with tryptamine to form a radioactive carboline derivative. The occurrence of this sequence in leukocytes is suggested by data that show that the enzyme reaction is strongly stimulated by addition of flavin adenine dinucleotide and that the final product is chromatographically identical to the adduct formed in the reaction of [14C]formaldehyde with tryptamine. In the absence of tryptamine, a product accumulates that can react with other HCHO acceptors, i.e., beta-phenylethylamine and dimedone; another reaction product is tetrahydrofolate. Production of formaldehyde is relatively more active in normal lymphocytes than in normal granulocytes, but it is even higher in lymphocytes of chronic lymphocytic leukemia. Activity in granulocytes from a subject with chronic myelocytic leukemia is also elevated but to a lesser extent than activity in lymphocytes of chronic lymphocytic leukemia. Activity in granulocytes from a subject with chronic myelocytic leukemia is also elevated but to a lesser extent than activity in lymphocytes of chronic lymphocytic leukemia. Formaldehyde production in leukocytes is only slightly stimulated by addition of various cobalamins, and activity is normal in leukocytes from a vitamin B12-deficient patient. We conclude that the system is cobalamin independent. Thus, there exists an active pathway from N5-methyltetrahydrofolate to tetrahydrofolate other than the one catalyzed by cobalamin-dependent N5-methyltetrahydrofolate-homocysteine methyltransferase.
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PMID:Production of formaldehyde from N5-methyltetrahydrofolate by normal and leukemic leukocytes. 1 82

Thymidylate kinase derived from the blast cells of human chronic myelocytic leukemia was purified 2186-fold to near homogeneity by means of alcohol precipitation, alumina-Cgamma gel fractionation, calcium phosphate gel fraction, ultrafiltration, and affinity column chromatography. The molecular weight was estimated by glycerol gradient centrifugation to be 50,000. This enzyme had an optimal activity at pH 7.1 and required a divalent cation in order to catalyze the reaction. Mg2+ and Mn2+ were found to be the preferential divalent cations. The activation energy was estimated to be 19.1 kcal/mol at pH 7.2. Initial velocity study suggested that the reaction followed a sequential mechanism. Mg2+ ATP had a Km of 0.25 mM and dTMP had a Km of 40 micrometer. The enzyme was unstable even at 4 degrees. In the presence of ATP or dTMP the enzyme maintained its activity. Purine triphosphate nucleosides were found to be better phosphate donors than the pyrimidine triphosphate nucleosides. ATP and dATP had a lower Km and a higher Vmax than GTP and dGTP. dTMP was the only preferred phosphate receptor among all the monophosphate nucleotides tested dTTP and IdUTP competed with both substrates and inhibited the reaction with a Ki of 0.75 mM and 1.1 mM, respectively.
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PMID:Human thymidylate kinase. Purification, characterization, and kinetic behavior of the thymidylate kinase derived from chronic myelocytic leukemia. 1 69

We have stored at -196 degrees C peripheral blood buffy coat (BC) and bone marrow (BM) cells collected from 47 patients with chronic granulocytic leukaemia in the chronic phase. Dimethyl sulphoxide (DMSO) 10% was used as cryoprotective agent. As these cells include CFUc and probably pluripotential stem cells they may be transfused as part of the management of patients who enter blast cell transformation. The mean numbers of nucleated cells collected and stored per procedure was about 9 times greater for BC collections than for BM harvests (106 +/- 49 (SD) X 10(9) versus 11.9 +/- 6.6 X 10(9) respectively). Agar CFUc assay showed that stored cells may remain viable for up to 5 years. Since in vitro studies showed that CFUc proliferation is not inhibited by low concentrations of DMSO the removal of all DMSO during cell reconstitution before transfusion may not be necessary. If autologous BC cells are capable of repopulating the BM of patients treated for CGL in blast cell transformation the routine collection and storage of BC rather than BM cells may be desirable for all newly diagnosed patients.
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PMID:Collection, cryopreservation and subsequent viability of haemopoietic stem cells intended for treatment of chronic granulocytic leukaemia in blast-cell transformation. 3 Apr 69

The treatment of elderly patients, who suffer from leukemia must not be standardized. Impaired bone marrow function, cardiovascular disease and other organopathias require an individually adapted therapy. The aim of treatment should be a good quality of life and not a remission at any price. Aggressive therapy in cases of acute leukemia with little progress should be avoided in favour of symptomatic treatment. CLL are treated in the progressive state of disease. Haemolytic anaemia and recurrent infections may complicate the course of CLL. CML is not a disease of old age but when it occurs intermittent therapy with cautious dosage is preferable to a continuous therapy.
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PMID:[Treatment of leukemia in the elderly (author's transl)]. 3 67

Possible predictive criteria of the refractoriness to therapy of the blastic phase of Ph-1-positive chronic granulocytic leukemia (CGL) have been sought. Eight cases in the blastic phase were studied. The blasts were noted to be of two types: some displayed a high nuclear:cytoplasmic ratio with deep blue cytoplasm, while others had a comparatively low nuclear:cytoplasmic ratio and bluish gray cytoplasm containing a few small granules. Electron microscopic studies showed a variety of features, including defective organelles and giant mitochondria. Cytochemical staining revealed the majority of blast cells to be peroxidase- and Sudan black-negative; granular PAS positivity was the rule. Serial cytogenetic studies demonstrated increasing aneuploidy. Bone marrow biopsy showed myelofibrotic changes in two cases. Two patients entered complete remission with prednisone and vincristine and with Ara-C and thioguanine, respectively. It is concluded that the blastic phase of CGL may manifest heterogeneity.
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PMID:Heterogeneity of morphological, cytochemical, and cytogenetic features in the blastic phase of chronic granulocytic leukemia. 4 88

To determine whether decreased alkaline phosphatase activity in the granules from neutrophils of patients with chronic myelogenous leukemia (CML) was due to an absence of enzyme or the production of defective enzyme, we compared the immunologic properties of granule alkaline phosphatase derived from patients with CML with that of normal subjects and patients with polycythemia vera (PRV). Antisera prepared in rabbits against granule alkaline phosphatase purified from the neutrophils of a patient with PRV produced a single precipitin line of antigenic identity when reacted with extracts of normal, PRV, and CML neutrophil granules. A histochemical stain for alkaline phosphatase activity (alpha-naphthyl acid phosphate coupled with Fast Blue RR) specifically stained the precipitin line. A variety of quantitative precipitin techniques failed to produce satisfactory precipitation of alkaline phosphatase activity. Comparative analyses were therefore performed by affinity chromatography using goat antirabbit-gammaglobulin linked to Sepharose 4B to adsorb alkaline phosphatase complexed with rabbit gamma globulin. With this method, 100% of CML, normal, and PRV alkaline phosphatase could be adsorbed. Using limiting concentrations of antibody, a proportionally smaller fraction of enzyme activity was absorbed as the concentration of PRV alkaline phosphatase or normal alkaline phosphatase was increased. Extracts of CML granules containing comparable amounts of protein but 200-fold less alkaline phosphatase activity per milligram did not specifically reduce adsorption. Thus, in CML, we found no evidence that the granulocytes contained a large amount of antigenically normal but enzymatically defective alkaline phosphatase. Examination of electron micrographs revealed no significant differences in the number or distribution of granules in the granulocytes of normal subjects or patients with PRV or CML. This suggests that the low level of neutrophil alkaline phosphatase in CML granulocytes is the result of decreased enzyme content and not a consequence of synthesis of catalytically defective enzyme.
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PMID:Neutrophil alkaline phosphatase: comparison of enzymes from normal subjects and patients with polycythemia vera and chronic myelogenous leukemia. 4 59

A cytogenetic anomaly consisting in the replacement of a 17 by its long arm isochromosome was identified as the only alteration in the marrow cells of two patients with acute granulocytic leukemia. In one case, the specific nature of the abnormal chromosome was established by newly available techniques. Since its identification in 1965, this structural anomaly, which implies 17 long arm duplication and short arm deletion, has been observed, as a sole or as an associated finding, in the malignant cells of a spectrum of blood disorders, including acute granulocytic leukemias, the blast crisis of chronic myeloid leukemia and lymphoreticular proliferative disorders. Attention is called to this particular rearrangement for its clinical as well as fundamental implications, as its presence in blood forming cells unfailingly hearalds a fast, fatal course of evolution.
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PMID:17 long arm isochromosome. A common anomaly in malignat blood disorders. 5 44

A report is presented on the changes of cytochemical reactions of neutrophilic granulocytes in children during acute leukaemia. Various hydrolases revealed a significant increase of activity during the acute stage of disease. The enzyme activity begins to decrease in remission, but regains its normal value only in the activity of alkaline granulocytic phosphatase. The glycogen content of granulocytes is reduced at the beginning of the disease and during the recidive as well as in the granulocytes of children affected with chronic myeloid leukaemia. The enhanced enzyme activity of granulocytes refers to the fact that the defence function of cells in acute leukaemias is not completely cancelled. Only a decreased glycogen content of cells refers to a disturbance in the metabolism of granulocytes.
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PMID:[Cytochemistry of leukocytes in children. II. Changes in cytochemical reactions of neutrophil granulocytes in the course of leukoses]. 5 Sep 63


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