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)

Deoxycytidine kinase, which phosphorylates deoxycytidine (CdR) and its analog, cytosine arabinoside (ara-C), has been purified 71-fold from human leukemic cells. Biochemical properties of the partially purified enzyme included a molecular weight of 68,000, Kms of 7.8 muM for CdR and 25.6 muM for ara-C, and optimal activity with ATP and GTP as phosphate donors. Ara-C phosphorylation was strongly inhibited by CdR (Ki = 0.17 muM) and dCTP (Ki = 7.3 muM) and was weakly inhibited by ara-CTP (Ki = 0.13 mM). Purification by calcium phosphate gel elution and DEAE chromatography effectively separated this enzyme from cytidine deaminase, which deaminates both CdR and ara-C, and from uridine-cytidine kinase, the enzyme which phosphorylates 5-azacytidine. CdR kinase activity was found to decrease and cytidine deaminase to increase with maturation of normal and leukemic granulocytes. Myeloblasts purified by Ficoll sedimentation revealed an average kinase activity of 15.4 U/mg protein in acute myelocytic leukemia and 12.3 U/mg protein in blastic crisis of chronic myelocytic leukemia (CML). The average ratio of CdR kinase to deaminase activity in crude cell extracts varied from 0.197 in AML and 0.089 in blastic crisis to 0.0004 in normal granulocytes, reflecting the changes which take place with cellular maturation. The absolute levels of kinase and deaminase and the ratio of these two enzymes varied considerably among patients with AML, indicating that quantitative differences may be found in the metabolism of CdR and its analogs in leukemic cells.
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PMID:Deoxycytidine kinase: properties of the enzyme from human leukemic granulocytes. 5 55

Rabbit or goat antisera directed to ALL, CLL, AML and CML cells were investigated in cytotoxicity tests with different leukaemia and normal cells as targets. After absorptions with erythrocytes and spleen cells from allogeneic donors the antisera killed only leukaemia cells. There was no reaction with remission leukocytes or blood leukocytes from normal donors. Anti-ALL-Sera reacted in 35 out of 49 tests with ALL cells from 13 patients. Apparently the ALL antisera which were directed to the T cell subtype of ALL preferentially affected ALL cells of this subtype. Cross reactions with cells from CLL, AML and CML were not found. Anti-CLL-sera reacted in 10 out of 12 tests with CLL cells from 4 donors, and in 4 out of 20 tests with ALL cells from 7 donors and also with the cells of a CML patient. AML cells from two patients were not killed. Antisera against AML and CML showed extensive cross reactions with cells of myelocytic and lymphocytic leukaemias. Absorption tests demonstrated the presence of two antibody specificities in AML antisera, one of which being directed to a common antigen of AML and ALL cells and another against an antigen of myelocytic leukaemia cells.
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PMID:Specificities of heterologous antisera against human leukaemia cells. 1. Reactions against leukaemia cells. 8 65

Antisera against human acute myelocytic leukaemias were tested in complement-dependent in-vitro cytotocity tests against leukaemia cells and normal cells as targets. After absorption with erythrocytes and spleen cells from allogeneous donors the antisera reacted with leukaemia cells, but not with leukocytes from bone marrow and the peripheral blood of children in remission, lymphocytes from healthy donors, enriched B-lymphocytes, enriched T-lymphocytes, PHA-induced blasts and cord blood lymphocytes. Extensive cross reactions were obtained in the tests against leukaemia cells. The antisera reacted not only with AML cells, but also with ALL, CLL, and CML cells. It was possible to remove the cross-reactivity with ALL cells through absorption with ALL cells or with fetal tissue, and to remove the cross reactivity with CLL cells through absorption with CLL. A complete absorption of the anti-AML sera was possible with AML and CML cells. After absorption with fetal tissue and CLL cells the antisera showed exclusively specificity for myelocytic leukaemias. Thus, AML cells contain three leukaemia-associated membrane antigen components: an antigen of fetal origin, a "CLL-specific" antigen, and an antigen that occurs on myelocytic leukaemias.
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PMID:Human leukaemia-associated antigens expressed by acute myelocytic leukaemia cells and their detection by heterologous antisera. 8 82

Antisera from rabbits and goats against subtypes of acute lymphocytic leukaemia (ALL with T-cell markers, ALL with B-cell markers, Non-T-non-B ALL) were tested for their specificity in complement-dependent in-vitro cytotoxicity testing. After absorption of the fivefold diluted antisera with erythrocytes and spleen cells of allogenous donors they reacted with ALL cells, but not with leukaemias of other types (AML, CLL, CML), lymphocytes of healthy donors, enriched B-lymphocytes, enriched T-lymphocytes, PHA-stimulated lymphocytes, cord lymphocytes and bone marrow lymphocytes of patients in remission. In the reactions of the antisera against ALL cells the subtype of ALL is of major importance: Six rabbit antisera and one goat antiserum against T-subtype ALL reacted in all 19 tests with the leukaemia cells of 5 patients with T-cell ALL and in all 9 tests with thymocytes of 3 donors, but only in 14 out of 41 tests with the leukaemia cells of 14 Non-T-non-B ALL patients. One antiserum against a B-subtype ALL lysed B-cell ALL (1/1), but not T-cell ALL (0/3), Non-T-non-B-cell ALL (1/5) and thymocytes (0/2). Four antisera against Non-T-non-B-subtype ALL reacted in 22 out of 46 tests with the Non-T-non-B cells of 17 ALL patients, but did not react with the leukaemia cells of 4 children with T-cell ALL (0/16), one child with B-cell ALL (0/1) thymocytes of 2 donors (0/4). The reactions of the anti-ALL sera with fetal liver cells, complete absorbability of the antileukaemic activity of the antisera with fetal tissue and the reactions of an anti-fetal serum with ALL cells point to the existence of fetal antigen components as leukaemia-associated antigens.
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PMID:Human leukaemia-associated antigens expressed by acute lymphocytic leukaemias and their detection with heterologous antisera to T, B-, and non-T-non-B subtype AL blasts. 8 83

The incidence of amoeboid movement configuration (AMC), a cell shape suggestive of cell locomotion at the moment of fixation, has been studied in the tumour cells of bone marrow smears from leukaemia patients at the time of diagnosis. The groups of patients with CML (n = 8), ALL (n = 5) and CLL (n = 9) were small, and the incidences of AMC were close to those found in the corresponding cell lines from healthy probands. In 39 patients with AML, the incidence of AMC was higher than in the other cell lines investigated. A positive skew distribution of AMC values and a positive significant correlation between incidence of AMC were found at the time of diagnosis and subsequent survival of the patients with AML, in spite of differences in treatment. It is suggested that this positive correlation may be due to an immune reaction of the patients against their tumour cells.
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PMID:Amoeboid movement configuration in tumour cells of bone marrow smears from patients with leukaemia. Incidence and significance. 26 78

Cellular recovery, maturation, and colony-forming cell (CFC) generation patterns of bone marrow cells from 23 patients with acute, subacute, and chronic myeloid leukemia (AML, SML, and CML) were studied using liquid and agar culture techniques. Increased recovery of proliferative myeloid cells from liquid culture was noted in 6 of 8 AML patients at diagnosis or relapse and 5 of 7 untreated SML patients. Patients with either AML or SML with rapid clinical progression exhibited greater recovery of cells in vitro with less maturation than patients with more stable disease. Studies from 3 patients with CML showed normal to increased cellular recovery with normal maturation. Three of 4 studies of AML patients followed sequentially in apparent remission, but with impending relapse, exhibited increased numbers of myeloblasts and promyelocytes, whereas 28 of 32 studies performed during stable remission were normal. The normally observed increase in CFC during liquid culture was absent in most leukemic marrow samples studied (3 of 4 AML, 4 of 6 SML, and 2 of 3 CML). Persistent low recovery of CFC during AML remission was associated in 3 patients with short remission duration. These studies indicated the potential utility of these techniques for the clinical evaluation of patients with myeloid leukemia and for studying factors involved in the progression of these diseases.
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PMID:Divergent patterns of marrow cell suspension culture growth in the myeloid leukemias: correlation of in vitro findings with clinical features. 26 54

Forty patients with chronic myeloid leukemia diagnosed and treated at the Chaim Sheba Medical Center, Tel-Hashomer, during the period 1966-76 were reviewed. All the patients were treated initially with busulfan (MYLERAN). Asymptomatic patients or those whose blood counts were stable and remained below 50,000/microliter were not treated. Maintenance therapy was not prescribed as a routine. The median survival time of all the patients was over 60 months--longer than reported in the literature. Prognostic parameters for longer survival were found to be Hb level greater than 10 g/dl at the time of diagnosis (P = 0.04) and duration of first remission in the chronic stage more than six months (P = 0.03). A borderline trend for better survival was found in patients with initial platelet counts above 100,000/microliter (P = 0.07).
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PMID:A retrospective study of patients with chronic myeloid leukemia diagnosed and treated at the Chaim Sheba Medical Center during the years 1966-76. 28 48

The phenomenon of premature chromosome condensation (PCC) was used to compare the bone marrow proliferation characteristics of 163 patients with various forms of leukemia prior to the initiation of new therapy. The proliferative potential index (PPI, or fraction of G1 cells in late G1 phase) and the fraction of cells in S phase was determined and compared to the type of disease and the bone marrow blast infiltrate for each patient. Previously untreated patients with acute leukemia exhibited an average PPI value three times that of normal bone marrow (37.5% for acute myeloblastic leukemia [AML], acute monomyeloblastic leukemia [AMML], or acute promyelocytic leukemia [APML] and 42% for acute lymphocytic leukemia [ALL] or acute undifferentiated leukemia [AUL]). Untreated chronic myelogenous leukemia (CML) patients showed intermediate PPI values (25.2%), whereas CML patients with controlled disease exhibited nearly normal PPI values (14.6%). On the other hand, blastic-phase CML patients exhibited PPI values closer to that observed in patients with acute leukemia (35.4%). Seven patients with chronic lymphocytic leukemia (CLL) exhibited even higher PPI values. No correlations were observed between PPI values, fraction of cells in S phase, and marrow blast infiltrate. For untreated acute disease patients, PPI values were prognostic for response only at low and high PPI values. These results suggest that the PCC-determined proliferative potential is a biologic reflection of the degree of malignancy within the bone marrow.
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PMID:Premature chromosome condensation studies in human leukemia. I. Pretreatment characteristics. 29 41

Sixteen chronic myeloid leukaemia (CML) patients in remission were tested with solubilized membrane antigens from CML leukaemic cells, CML blasts, AML blasts and ALL blasts for cellular immunity in vitro by lymphocyte transformation (LT) and leucocyte migration inhibition (LMI) assays. Twelve CML patients in remission were tested with allogeneic PHA-transformed normal lymphoblasts. As controls, peripheral-blood leucocytes from 9 healthy persons were tested with the same antigen preparations. It was seen that 8/16 (50%) CML patients responded to CML antigens by both LT and LMI assays, while 5/16 (31%) patients reacted to CML blasts and 44% (7/16) patients reacted to AML blast antigens. It was interesting to note that 5/11 (45%) CML patients reacted to ALL blast antigens by both assays. One out of 12 patients reacted to PHA-transformed lymphoblasts. None of the healthy controls reacted to leukaemia-associated antigens. The results suggest the sharing of antigens between myeloid leukaemic cells, myeloid blasts and lymphoid blasts.
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PMID:Cellular sensitization in chronic myeloid leukaemia patients to leukaemic blast antigens. 29 50

Bone marrow (BM) karyotypes from 16 consecutive children presenting with nonlymphocytic leukemia were established with the use of banding techniques, before therapy. The two patients with chronic myeloid leukemia (CML) showed the Philadelphia (Ph1) translocation (9q+;22q-). Five of the 14 patients with an acute nonlymphocytic leukemia (ANLL) presented no acquired cytogenetic abnormalities, but one of these five showed a high level of hypodiploidy. One patient with AML evidenced a variant of the Ph1 chromosome originated as a translocation (12p+;22q-). Nonrandom abnormalities (-7; 7q-; +8; t(8;21); -21) were found in six patients, isolated or in association with otheraberrations. Among the random abnormalities, apparently balanced translocations and chromosomal deletions were observed. In ANLL, no correlation could be found between morphologic diagnosis and cytogenetic findings. On the other hand, the presence of BM cells with a normal karyotype at diagnosis was associated with an improved remission rate and survival time. Followup studies were performed in four ANLL patients with an abnormal cell clone at diagnosis. Three of them achieved hematologic remission; their BM karyotype was found to be normal at that stage. In the 4th patient, generalization of the abnormal karyotype in BM cells was seen in the terminal phase of the disease.
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PMID:Bone marrow karyotypes of children with nonlymphocytic leukemia. 29 69


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