Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chromosome abnormalities, sister chromatid exchanges (SCE), and cell cycle kinetics were studied in phytohemagglutinin-stimulated lymphocytes from 8 adult T cell leukemia (ATL) patients. In all these cases, chromosome abnormalities were observed in 5-day PHA-stimulated cultures. Four cases had characteristic marker chromosomes; two were due to a balanced translocation, t(9;21), and two to a simple deletion, 5p-. The other four cases, however, had rather complicated chromosome abnormalities, e.g., 1q+, 2q+, 5q+, 6q-, 14q+, 10p-. When chromosome abnormalities were analyzed in previously reported cases, the abnormalities were mostly distributed among chromosomes #1, #2, #5, #6, #14, and #21. These findings suggest that the abnormalities involving #1, #2, #5, #6, #14, and #21 are intimately related to ATL. The SCE frequency was in the normal range in ATL cells. Cell cycle analysis revealed that the duration of two cell cycles in cells labeled with bromodeoxyuridine (BrdU) required approximately 80 hr in ATL cells, whereas the time of two cell cycles in normal cells is 40 hr. These findings indicate that the ATL cell cycle time is about 40 hr, about double that of normal cells (20 hr), in PHA-stimulated cultures. ATL has been known to be a mature T cell leukemia and to respond poorly to chemotherapy. The latter may be due to the elongated cell cycle or to the mature characteristics of the leukemic cells. The association of ATL with cutaneous T cell lymphoma is also discussed.
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PMID:Chromosome abnormalities, sister chromatid exchanges, and cell cycle analysis in phytohemagglutinin-stimulated adult T cell leukemia lymphocytes. 387 51

An IgM monoclonal antibody directed against the T-cell E-rosette receptor was obtained by preparing a hybridoma against cells of a human T-cell leukemia line, HPB-ALL. The antibody, named EDN-34B1, reacts exclusively with cells of T-cell lineage, including those of three T-cell leukemia lines. It does not react with cells of B-cell lines, normal B-cells, or monocytes. EDN-34B1 recognizes a single polypeptide of approximately 50,000 molecular weight, is capable of blocking E-rosette formation, and its binding to the target cell can be specifically blocked by monoclonal antibodies 9.6 and OKT-11, both anti-E-receptor antibodies. EDN-34B1 is 100% cytotoxic against normal thymocytes and peripheral T-cells, thus enabling the routine removal of such cells from a mixed lymphocyte population, and kills a higher percentage of normal T-lymphocytes than Ab 9.6, even though immunofluorescence studies have shown that both antibodies bind to the same fraction of PBLs. This phenomenon may be due to the IgM nature of EDN-34B1. Addition of EDN-34B1 and complement to PBLs totally abrogates T-cell functions such as mitogen (PHA) stimulation and response in MLR, while addition of EDN-34B1 alone only affects MLR.
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PMID:An IgM pan-T monoclonal antibody that blocks E-rosette formation. 387 45

5-Ethyl-2'-deoxyuridine (5EtdUrd) is a biologically active thymidine analogue. The cytotoxicity of 5EtdUrd was investigated with seven established human leukemia cell lines as well as with human peripheral blood PHA-stimulated lymphocytes. All types of leukemia cells were susceptible to the toxicity of 5EtdUrd as assayed with a [U-14C]-L-leucine incorporation system developed for this study. A 50% inhibition of leucine incorporation in 3-day cultures was induced by 1.3-3.8 microM 5EtdUrd with leukemic cells, but the concentration required to induce similar inhibition with PHA-stimulated lymphocytes was approximately was approximately 100-fold. The toxicity of 5EtdUrd seemed to require active DNA synthesis, since the inhibition of leucine incorporation became obvious only after the first 24 hours of culture. The DNA incorporation studies were based on a new isotopically labeled 5EtdUrd derivative, [2-14C]5EtdUrd, synthesized for this study in our laboratory. It was demonstrated for the first time that most of the radioactivity derived from [2-14C]5EtdUrd in DNA was in 5-ethyluracil. 5EtdUrd has a powerful antileukemic potency in vitro. Its effects against human leukemia in vivo remain to be tested.
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PMID:5-Ethyl-2'-deoxyuridine. Cytotoxicity and DNA incorporation demonstrated with human leukemic cells and PHA-stimulated lymphocytes in vitro. 387 44

A patient with CML in chronic phase was admitted to our center for bone marrow transplantation. Cytogenetic analysis of bone marrow cells revealed a Ph chromosome due to a standard t(9;22) and a Robertsonian t(14;15). This Robertsonian translocation was also found in PHA-stimulated lymphocytes of the patient's sister, the donor of the bone marrow. A chromosome study of the whole family proved the constitutional character of the t(14;15) abnormality and showed that it was inherited from the father's side. All family members were phenotypically normal with normal mental status. Female carriers of the t(14;15), as well as wives of male carriers, had a high incidence of miscarriages and early death of their offspring. The occurrence of Ph-positive CML in a patient with a Robertsonian t(14;15) might indicate increased risk for the development of leukemia in patients with this constitutional chromosome abnormality. This assumption however, is limited by the rarity of the Robertsonian translocations.
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PMID:Ph-positive CML in a family with a constitutional Robertsonian translocation 14;15. 390 9

The optimal concentration of leukocytes for maximizing the yields of metaphase cells was examined using PHA-stimulated and unstimulated peripheral blood cells of various leukemic patients with hyperleukocytosis, including 5 acute nonlymphocytic leukemias, 4 Ph-positive chronic myelocytic leukemias, one acute lymphoblastic leukemia, and one malignant lymphoma at a leukemic phase. The yields of metaphases reached maximum at leukocyte concentrations of either 1 X 10(6) or 2 X 10(6)/ml in both stimulated and unstimulated blood cultures of each patient, except for one patient with malignant lymphoma who exhibited no metaphases at any cell concentration level in the unstimulated culture. Metaphase yields in the stimulated and unstimulated cultures correlated with neither the percentages of blast cells and lymphocytes in the peripheral blood of the leukemia patients nor with the type of leukemia studied.
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PMID:Leukocyte concentration and the yields of metaphase cells in cultured peripheral blood of leukemic patients with hyperleukocytosis. 398 51

5-Hydroxymethyl-2'-deoxyuridine is a biologically active thymidine analogue. This investigation was aimed at characterizing the cytotoxicity of 5-hydroxymethyl-2'-deoxyuridine and its incorporation into DNA. Fifty percent inhibition of cellular proliferation, assessed by incorporation of [U-14C]-L-leucine in vitro, was caused by 1.7-5.8 X 10(-5) incorporation of [U-14C]-L-leucine in vitro, was caused by 1.7-5.8 X 10(-5) M 5-hydroxymethyl-2'-deoxyuridine in seven human leukemia cell lines. Higher concentrations of 5-hydroxymethyl-2'-deoxyuridine, i.e. 6-8 X 10(-5) M, were required for a comparable inhibition in human PHA-stimulated peripheral blood lymphocytes. A new synthesis procedure for [2-14C]5-hydroxymethyl-2'-deoxyuridine was developed. The net incorporation of [2-14C]5-hydroxymethyl-2'-deoxyuridine into DNA of hematopoietic cells was low. The possibility of a repair mechanism for 5-hydroxymethyluracil bound to DNA is discussed.
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PMID:5-Hydroxymethyl-2'-deoxyuridine. Cytotoxicity and DNA incorporation studied by using a novel [2-14C]-derivative with normal and leukemic human hematopoietic cells. 406 Sep 61

Sera from 16 of 20 patients with AML at some stage of the disease inhibited the in vitro PHA transformation of normal lymphocytes assessed by measuring the rate of DNA synthesis after 67-70 hours; 42% of pretreatment sera were inhibitory. Inhibitory activity was overcome at PHA concentrations 2-3 times greater than the concentration which allowed maximum discrimination between NHS and leukaemia sera.PHA transformation of washed lymphocytes obtained from AML patients before treatment and when receiving induction or consolidation (cytoreductive) chemotherapy was reduced only when cultures contained a high proportion of primitive cells. Even in primitive cell contaminated cultures significant responses to PHA could be measured if conditions were modified to prevent increasing acidity.Reports of reduced in vitro immunological reactions in pretreatment and poor prognosis patients may therefore be due to the presence of primitive cells in culture, and in treated patients to the failure of chemotherapy to reduce the circulating primitive cell count. Serum inhibitory factors may have a significant immunosuppressive effect in vivo, but the accurate assessment of the role of immune mechanisms in AML should attempt the measurement of specific immunity.
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PMID:Immunological studies in acute myeloid leukaemia: PHA responsiveness and serum inhibitory factors. 451 88

Assays of lymphocyte subpopulations and function have been performed on patients with acute lymphoblastic leukaemia still in remission after 18 months' treatment. The patients were subjects of a trial of the value of craniospinal irradiation in the third month of treatment in preventing central nervous system relapse. Effects of both irradiation and chemotherapy were observed. Lymphopenia was much more marked in those patients who had received irradiation over a year previously. Assays of response to phytohaemagglutinin (P.H.A.) and staining for surface immunoglobulin indicated that this difference was due to a deficiency in thymus-dependent lymphocytes in the irradiated children. Chemotherapy had a particularly marked depressant effect on lymphocytes with antibody-dependent cytotoxic activity and a proportion of PHA-responsive cells were also depressed. It may be relevant that four of the patients depleted of thymus-dependent lymphocytes by radiation died of infection during remission, while none of those treated with chemotherapy alone died in remission.
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PMID:Immunosuppressive consequences of radiotherapy and chemotherapy in patients with acute lymphoblastic leukaemia. 457 43

PHA-stimulated peripheral lymphocytes from six healthy adults consisting of four family members of an adult T-cell leukemia (ATL) patient and two blood bank donors, seropositive to ATL-associated antigens (ATLA), were all positive for the expression of ATLA and ATL-associated virus (ATLV). These results revealed that anti-ATLA-positive persons were healthy carriers of ATLV and that the numbers of ATLV observed in each culture were more proportional to the percentage of ATLA-positive lymphocytes than anti-ATLA titers of each person. Virus particles detected were C-type in morphology, and essentially similar to those observed in MT-2 and other ATL-related cells, but rather uniform in size, mostly 120-130 nm in diameter. Furthermore, it is of interest that tubuloreticular structures and striated fusiform structures, which were found in fresh or short term cultured ATL cells, were observed in some cultures of lymphocytes from anti-ATLA-positive healthy persons.
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PMID:Ultrastructural study of type C virus particles in phytohemagglutinin-stimulated lymphocytes from healthy adults seropositive to adult T-cell leukemia-associated antigens. 609 26

Human T-cell leukemia/lymphoma virus type I(HTLV-I) infection appears to be closely associated with the leukemogenesis of adult T-cell leukemia (ATL), although its mechanism remains unclear. Since our previous report that leukemic cells from patients with ATL expressed Tac antigen (Ag) (interleukin-2 (IL-2) receptor) on their cell surface, we have been studying IL-2 receptors on ATL leukemic cells to see whether they are different from normal IL-2 receptors and whether they play a role in the neoplastic growth of ATL cells. Peripheral blood leukemic cells from 35 patients with ATL expressed IL-2 receptors which were detected by anti-Tac monoclonal antibody when examined immediately after the separation of cells or after culture for 24 or 48 hr. The number of anti-Tac binding sites ranged from 4,300 to 11,400 in fresh cells and from 6,100 to 96,000/cell in short term cultured leukemic cells, whereas phytohemagglutinin-P(PHA-P)-stimulated normal T cells exhibited 7,000 to 35,000 anti-Tac binding sites/cell. HTLV-I-infected cell lines such as MT-1 and HUT-102 expressed a markedly enhanced number of Tac Ag molecules. Leukemic cells from 15 ATL patients showed no or very poor proliferative response to various concentrations of IL-2, although they expressed Tac Ag. Radiolabeled IL-2 binding experiments revealed that ATL leukemic cells could bind IL-2 although the number of IL-2 binding sites was much less than that of anti-Tac binding sites. IL-2 receptors on ATL cells, unlike normal activated T cells, were not modulated (down-regulated) by anti-Tac antibody.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Abnormal expression of interleukin-2 receptor (Tac antigen) in adult T-cell leukemia. 610 Jun 43


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