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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thymic lymphoma/leukemia is the major cause of death in B6C3F1 mice chronically exposed to 1,3-butadiene (BD). Similar to radiation-induced murine thymic lymphoma, the bone marrow is also a major target organ. Because of the association of murine thymic lymphoma with endogenous type-C murine leukemia retroviruses (MuLV) present in the germ line of most strains of laboratory mice, including B6C3F1 and its parent strains, we examined the effects of BD exposure on NIH Swiss mice which do not possess intact endogenous ecotropic MuLV. Male NIH Swiss mice exhibited a macrocytic-megaloblastic anemia following inhalation of 1250 ppm BD for 6 weeks. Treatment-related changes included decreases in circulating erythrocytes, total hemoglobin, and hematocrit and an increase in mean corpuscular volume. An eightfold increase in circulating micronuclei was also observed. The anemia was not accompanied by a significant alteration in mean corpuscular hemoglobin concentration, an increase in circulating reticulocytes, or an increase in circulating nucleated erythrocytes. These findings are consistent with a treatment-related macrocytic-megaloblastic anemia and indicate that the bone marrow is an important target for BD toxicity in mice independent of MuLV background and expression.
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PMID:Macrocytic-megaloblastic anemia in male NIH Swiss mice following repeated exposure to 1,3-butadiene. 302 Jul 40

The risk of development of CNS leukemia was investigated in 153 adults with acute lymphocytic leukemia (ALL) who received systemic combination chemotherapy without CNS prophylaxis. Overall, 31 patients (20%) developed CNS leukemia after a median of 6 months of therapy; the estimated 1-year incidence of CNS leukemia was 21% (SE, 3.9%). Characteristics significantly associated with CNS involvement included the presence of elevated hemoglobin creatinine, alkaline phosphatase, fibrinogen, and lactic dehydrogenase levels; B-cell leukemia; and high leukemic cell proliferative activity. Multivariate analysis identified lactic dehydrogenase levels of greater than or equal to 600 U/L and greater than or equal to 14% of cells in the S + G2M compartment to have independent additive poor prognostic significance. Patients were categorized into different risk groups for CNS leukemia with 1-year incidences ranging from 4% to 55%. While related to a high occurrence of CNS leukemia at diagnosis (33%) and subsequently (100%), the low incidence of B-cell disease excluded it from the multivariate analysis. The use of systemic chemotherapy containing multiple agents with good CNS penetration and in high doses (VAD regimen) in 90 patients was associated with a trend for lower CNS leukemia at 1 year (15% v 31%), especially in the low-risk category. We propose to develop future therapies for adults with ALL that include risk-oriented CNS prophylactic approaches.
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PMID:Identification of risk groups for development of central nervous system leukemia in adults with acute lymphocytic leukemia. 305 30

Proliferation and differentiation are inversely related in many cell culture systems. The study of inducible systems is facilitated by optimal growth conditions in order that whatever differentiation is observed may be attributed to a specific effect of the inducer, rather than to a nonspecific effect of adverse growth conditions. To investigate the role of CO2 supply in an inducible system, the K562 human leukemia cell line inducible for hemoglobin synthesis was studied at 10%, 5% and 1.5% CO2 concentrations. The lower the CO2 concentration, the higher the percentage of benzidine-positive cells but the slower the growth rate. This increase in benzidine positivity reflected hemoglobin synthesis as indicated by incorporation of 3H-leucine into globin chains. If, in addition to reducing CO2 concentration, the complete medium was replaced by a bicarbonate-free medium, the percentage of benzidine-positive cells was further increased and growth further slowed. However, if endogenously produced CO2 was retained by sealing the culture vessel, these effects were mitigated. Since addition of ribosides blocked these effects, the mechanism for these effects appears to be inhibition of riboside biosynthesis due to the depletion of CO2 as a substrate. The implication of this work is that, for reproducibility in studies of inducible systems in which reduction of proliferation may itself increase the probability of differentiation, the CO2 tension, the bicarbonate concentration in the medium and the rate of egress of endogenously produced CO2 must be kept constant.
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PMID:Induction of hemoglobin synthesis in K562 cells by carbon dioxide deficiency. 310 85

Using flow cytometric techniques, we determined the pretreatment distribution of DNA content in propidium iodide-stained leukemic blasts from 205 children with "standard-risk" acute lymphoblastic leukemia (ALL). Risk assignment was based on an initial WBC count less than 100 X 10(9)/L, no thymic mass, no meningeal leukemia, and lymphoblasts lacking sheep erythrocyte receptors or surface immunoglobulin. A single aneuploid leukemic line was detected in 74 cases (36.1%): 70 hyperdiploid and four hypodiploid. For hyperdiploid cases, the DNA index (DI, or ratio of the DNA content of leukemic v normal G0/G1 cells) ranged from 1.06 to 2.0 (median, 1.20). A secondary leukemic line with hyperdiploid cellular DNA content was identified in 21 cases with diploid primary lines. Children whose primary leukemic line showed a DI greater than or equal to 1.16 (n = 57) had significantly better responses to treatment than did those with either a diploid DI (n = 130; P = .002) or values in the range of 1.01 to 1.15 (n = 14; P = .001). The relative risk of failure for hyperdiploid cases with DI greater than or equal to 1.16, corresponding to greater than or equal to 53 chromosomes, was one-third that of the other two groups. Treatment responses of patients with both diploid and hyperdiploid lines were identical to those associated with single diploid lines, but significantly worse than those associated with single hyperdiploid lines with DI greater than or equal to 1.16 (P = .016). The most favorable prognostic variables selected by a Cox proportional hazards model were: DI greater than or equal to 1.16 (P = .001), white race (P = .022), WBC less than or equal to 25 X 10(9)/L (P = .032), age between 2 and 9 years (P = .075), and hemoglobin less than 7.0 g/dL (P = .094). DNA index greater than or equal to 1.16 retained its significant prognostic impact even after adjustment for other variables (P = .001). With the combination of DI greater than or equal to 1.16 and WBC less than or equal to 25 X 10(9)/L, one can identify a group of children with ALL who have a low probability of relapse when treated with current therapy. If they remain disease-free after longer follow-up, it may be advisable to treat them with less intensive, hence less toxic, chemotherapy than patients with higher WBC counts or lower DI values.
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PMID:Prognostic importance of blast cell DNA content in childhood acute lymphoblastic leukemia. 315 60

The human leukemia cell line K 562, when treated with subcytotoxic doses of hemin, undergoes reversible erythroid commitment, as shown by the increased synthesis of hemoglobin. Hemin-treated cells maintain replicative capabilities, although perturbations in cell cycle kinetics are induced. K 562 cells were used to investigate changes in antitumor drug sensitivity as a consequence of cell differentiation induced by hemin treatment. K 562 leukemia cells, cultured in the presence of 20 microM hemin for 12 days, were treated with non-phase-specific (adriamycin, 4-OOH-cyclophosphamide, mitomycin C, bleomycin, cis-diamminedichloro platinum) and phase-specific (vincristine, methotrexate and 5-fluorouracil) antitumor drugs. The results obtained by chemosensitivity tests showed a generalized decrease in chemosensitivity of the K 562 cells to all the drugs tested as a consequence of the hemin-induced differentiation.
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PMID:Changes in chemosensitivity of K 562 leukemia cells after induction of erythroid differentiation by hemin. 316 23

A low-dose Ara C (LDAC) regimen (0.2 mg/kg/d) was tried in two groups of eleven patients with MDS and in ten with hypoplastic leukemia (HL) proven by biopsy. In HL, seven patients achieved complete remission (CR), but CR duration was rather short (4-9 months). Some cases showing relapse could be induced back into CR by the LDAC regimen. All patients showed marked bone marrow aplasia before reaching CR. Therefore, the main effect of LDAC was considered to be cytotoxic activity. In one HL patient, the karyotype of 47, XX, +8 at diagnosis was converted to normal, 46, XX after CR. In MDS, there were no CR cases but five patients partially responded to the LDAC regimen. One patient died of cerebral hemorrhage soon after LDAC treatment. Three patients developed overt leukemia and in one of them the disease was well controlled by LDAC over thirty months. One patient with typical refractory anemia with excess blasts (RAEB) suffered severe bone marrow aplasia after 12 mg/d for 10 days of LDAC, but one month later his hematopoiesis gradually recovered and reached a normal hemoglobin level (12 g/dl). However, all of his karotypes showed 45, XY, -7 at that time. LDAC regimen is effective, especially for HL, but may have a limited effect on MDS.
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PMID:[Effect of low-dose Ara-C regimen on myelodysplastic syndrome (MDS)]. 316 77

Adult chronic myelomonocytic leukemia (CMML), as defined by the French-American-British (FAB) group, is associated with a variable survival, ranging from a few weeks to several years. From 1971 to 1986, we made the diagnosis of CMML in 107 cases, according to FAB criteria (except for patients with 20% to 30% bone marrow [BM] blasts who were also included). Median survival was 30 months (range 1 to 81 months) and life expectancy did not seem to be influenced by treatment modalities other than supportive care. Eighteen patients (17%) progressed to acute nonlymphoblastic leukemia (ANLL). In a Cox regression model, main factors associated with short survival were: an excess of marrow blasts (P = 10(-6], anemia (P = .17 x 10(-5], high peripheral blood (PB) monocytosis (P = .26 x 10(-5], presence of PB blasts (P = .49 x 10(-4], and to a lesser extent hyperleukocytosis (P = .001), presence of PB immature granulocytes, thrombopenia, and splenomegaly. Survival (less than 1 year v greater than 1 year) could be predicted at diagnosis in a multivariate stepwise discriminant analysis using two parameters only (percentage of BM blasts and hemoglobin level), with 82% accuracy. Among patients surviving greater than 1 year, initial PB leukocyte count was higher in patients with intermediate survival (12 to 42 months) than in long survivors (greater than 42 months) and was the only discriminating factor between these two subgroups in multivariate analysis. Abnormal cytogenetic findings and increased lysozymuria were also poor prognostic factors, but could not be analyzed in the multivariate models, as they were determined in a minority of patients. Parameters associated with subsequent progression to ANLL included younger age at diagnosis, thrombopenia, increased BM blasts, and splenomegaly. Our study allows for the identification of subgroups with different prognoses in CMML, on the basis of a small number of hematologic parameters, particularly initial percentage of BM blasts, hemoglobin level, and leukocytosis. These subgroups probably require different therapeutic approaches.
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PMID:Prognostic factors in adult chronic myelomonocytic leukemia: an analysis of 107 cases. 316 85

Three new cases of monosomy 7 are described. Two children, before onset of overt leukemia, had a preleukemic state: one with thrombopathy and myelodysplastic syndrome, the other with a moderate splenomegaly and an absolute monocytosis. In these two cases the leukemia was chemoresistant. The last child had a subacute myelomonocytic syndrome (juvenile type of chronic myelogenous leukemia) without high fetal hemoglobin value. She died from cachexia. The poor prognosis of monosomy 7 is underlined and such a chromosome deletion should be searched in myeloproliferative syndrome with monocytosis.
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PMID:[Bone marrow monosomy 7 in children]. 324 43

The present study has investigated the regulation of malignant phenotype and gene expression in a human promyelocytic leukemia cell mutant (HL-60-AR) by means of cellular engineering technique of cybridization between the fusions of the mutant cells with enucleated mouse reticulocytes. Results indicate that the cybrid cells (HL-R) incorporated with reticulocyte cytoplasts become differentiated, and the malignancy is obviously suppressed or reversed to a certain degree when compared with those of parental tumor cells. They lose the growth ability to form colony soft agar medium, become non-tumorigenic under heterotransplantation to nude mice, and are accompanied by decrease in growth rate, cellular mitotic index and DNA synthesis. No gene transcripts or homologous sequence of mRNA corresponding to c-myc oncogene can be detected in cybrid cells by Northern blot technique with cloned c-myc gene probe, suggesting that the expression of originally active c-myc has been inhibited. On the other hand, analysis, by the same molecular hybridization technique with human globin gene probe and by PAGE method, of the expression of globin gene products in cybrid cells detected at the transcription (globin mRNA) and translation (hemoglobin) levels demonstrates consistently that originally inactive human globin gene has been activated to express in passages. These results suggest that some regulatory factors existing in reticulocyte cytoplasm can regulate gene expression and reverse malignant phenotype of leukemia tumor cells.
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PMID:Studies on the regulation of malignant phenotype and gene expression in human promyelocytic leukemia cell mutant (HL-60-AR). 324 94

A 64-year-old man was found to have a hemolytic anemia with a hematocrit of 0.28 (28%) during a routine evaluation. One month before this his hematocrit had been normal. Further studies revealed a myelodysplastic syndrome and acquired hemoglobin H disease. Eighteen months later this transformed into acute megakaryoblastic leukemia with disappearance of hemoglobin H, and shortly thereafter he had myelofibrosis develop. Acquired hemoglobin H disease, which is an alpha-thalassemia-like syndrome, results in the formation of an unstable hemoglobin composed of beta chain tetramers. This condition has been associated with preleukemia, sickle cell anemia, and hematologic malignancies. Although idiopathic myelofibrosis also has been described as a setting in which this thalassemic syndrome occurs, the present case is unusual in that the myelofibrosis was preceded by refractory anemia with leukemic transformation.
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PMID:Myelodysplastic syndrome with acquired hemoglobin H disease. Evolution through megakaryoblastic transformation into myelofibrosis. 327 51


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