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)

Mice ingesting 30 to 50% D2O (heavy water, deuterium oxide) developed a dose-dependent depression of formed peripheral blood elements in 4 to 9 days. The principal mechanism of anemia and thrombocytopenia is impaired hematopoiesis. Despite pancytopenia in the peripheral blood, bone marrow cellularity and morphology remained normal. Upon replacement of D2O with tap water, platelet and neutrophil concentrations returned to normal within 48 to 72 hr. In contrast, blood lymphocyte concentrations remained low for several weeks. B-lymphocytes may be more affected by deuteration than other lymphocyte subsets. In vivo reticuloendothelial cell function, as assessed by 51Cr-labeled sheep erythrocyte clearance, was unaffected by D2O. Although a dose-dependent decrease in fluid intake occurred during deuteration, hematocytopenia was not a consequence of dehydration. In view of the known kinetics of D2O in biological systems, the rapid response of myeloid elements to deuteration must be due primarily to the solvent (nonmetabolic) isotope effect. Prolonged deuteration has proven toxic when included in regimens for treatment of neoplasia, including leukemia, in animal models. The present study shows that modulation of hematopoiesis by D2O is possible without invoking the toxicities associated with prolonged deuteration.
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PMID:Effects of deuteration on hematopoiesis in the mouse. 283 49

alpha-Difluoromethylornithine (DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase, was used alone and in combination with multiple doses of methylglyoxal-bis(guanylhydrazone) (MGBG) to treat mice with systemic L1210 leukemia. Used as a single agent (administered p.o. as a 3% solution in tap water), DFMO exerted a weak therapeutic effect against this tumor. The therapeutic effect of MGBG (administered i.p. at 50 mg/kg/day) was only slightly better. However, 1-3 days of pretreatment with DFMO strongly potentiated the effect of MGBG treatment. Thus, mice treated with the combination exhibited an increase in life span of up to 138%. The prolonged survival of leukemic mice treated with a combination of DFMO and MGBG was associated with inhibition of polyamine synthesis and a marked decrease in the spermidine and spermine content of the tumor cells as compared to untreated controls. As a consequence, there was a continuous decrease in the S- and G2-phase fractions with a concomitant increase in G1. Used singly, DFMO and MGBG had no significant effect on the cell-cycle distribution. The effects of the combination of DFMO and MGBG on the cell-cycle distribution are consistent with the contention that polyamine deficiency primarily interferes with initiation of DNA synthesis. However, the possibility that selective S-phase kill partly contributes to this change in cell-cycle distribution cannot be excluded.
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PMID:Synergistic antileukemic effect of two polyamine synthesis inhibitors. Host survival and cell-cycle kinetic analysis. 308 54

2 children with Down's syndrome showed severe anaemia, leucocytosis with blastic cells, thrombocytopenia and hepatosplenomegaly. Bone marrow aspirations were near-dry tap and marrow biopsy revealed primary myelofibrosis with myeloid metaplasia (MMM). Their course was short with a blood picture similar to that of leukaemia. They expired 2 months and 21/2 months after diagnosis, respectively. The cases were thought to represent an acute childhood variant of MMM. Cytogenetic study of circulating white cells by 24 h culture without phytophaemagglutinin stimulation revealed aneuploidy in both cases, the first case showing marked aneuploidy with a predominant karyotype of 50,XX,+8,+19,+19,+21 and the second case a mosaic of 47,XX,+G/48,XX+G,+G. The karyotype of phytohaemagglutinin stimulated lymphocytes was 47,XX,+G in both cases. These findings suggest that the abnormal karyotypes are those of circulating blastic cells which are abnormal clones of haematopoietic cells responsible for MMM. In Down's syndrome, MMM might not be so rare as reported.
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PMID:Primary myelofibrosis with myeloid metaplasia and cytogenetically abnormal clones in 2 children with Down's syndrome. 645 73

Therapy-related acute nonlymphocytic leukemias occur with increasing frequency owing to modern aggressive antineoplastic therapies. Out of 3,138 bone marrow trephine biopsies, there were 148 cases of acute nonlymphocytic leukemias. Of these, 14 cases occurred 30-156 months following chemotherapy or radiotherapy or both for malignant disease. The male/female ratio was 0.27 (vs. 1.6 of "de novo" leukemias). Primary malignancies (7 Hodgkin's disease, 1 fibrosarcoma and 6 carcinomas) had been treated with chemotherapy+radiotherapy (10 cases), with chemotherapy alone (3 cases) or with radiotherapy alone (1 case) and were apparently cured. All therapy-related leukemias were heralded by a preleukemic cytopenic phase. Response to therapy was poor (mean survival 3.9 months). Bone marrow histopathological findings showed in 13 cases acute myelo- or monoblastic leukemia and in 1 case erythroleukemia. Out of 21 biopsies, there were increased numbers of abnormal megakaryocytes in 10, megaloblastic dyserythropoiesis in 7, and fibrosis in 13 (moderate in 11 cases and severe in 2, with dry tap). Therapy-related acute leukemia appears to be a distinct clinical-pathological entity. Bone marrow trephine biopsy is useful because of the frequency of fibrosis, the possibility of dry tap, and the characteristic histopathological findings that make diagnosis possible also in the preleukemic phase.
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PMID:Bone marrow histopathology of acute nonlymphocytic leukemia following therapy for primary malignancies. 647 85

A series of 10 cases of hairy cell leukemia (HCL) in native Japanese patients was studied. The clinicopathological features and the phenotype of the leukemic cells were compared with those of HCL in Western countries. The clinical pictures were similar to those in Western countries but some hematological findings were different. The Japanese patients had more marked leukocytosis, less granulocytopenia and thrombocytopenia, and no dry tap on bone marrow aspiration. The phenotype of hairy cells was much the same in both areas. Two kinds of anti-hairy cell sera were raised in rabbits. One (AHS 406) was obtained from rabbits immunized by injecting whole hairy cells. The other (alpha HC-G and alpha HC-M) was obtained by injection of membrane glycoproteins partially purified from hairy cells. The reactivity of the former antiserum (AHS 406) against leukemic cells from a variety of leukemias including HCL and B-cell chronic lymphocytic leukemia was studied by an immunoprecipitation technique. AHS 406 defined three cell surface antigens on HCL, P-30, P-35 and GP-135 (30,000, 35,000 and 135,000 daltons respectively). These three components are expressed only on neoplastic B lymphocytes. Quantitative differences in expression were observed in different types of leukemia, although all three antigens were most strongly expressed in HCL. alpha HC-G showed reactivity similar to that of OKIa-1. alpha HC-M reacted with hairy cells but not with other leukemic cells except mature granulocytes of chronic myelocytic leukemia. It also reacted with most granulocytes and a few mononuclear cells in normal peripheral blood. Preliminary immunochemical studies suggest that alpha HC-M reacts with a glycoprotein with a molecular weight of 26,000.
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PMID:Hairy cell leukemia: a report of 10 cases in Japan and characterization of anti-hairy cell sera. 664 81

A 3-month-old male infant had bilateral redness of the eyes. Large, immature blast cells were noted in material obtained by anterior chamber tap, and the diagnosis of acute promonocytic leukemia was confirmed by bone marrow aspiration and autopsy. Detailed clinical, histopathological, histochemical, and electron microscopic studies were carried out. The case showed forcibly that children with sterile hypopyon should be investigated for malignancy.
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PMID:Acute promonocytic leukemia with ocular involvement. 693 Feb 1

Sixteen patients with chronic granulocytic leukaemia (CGL) in blast cell transformation (BT) were studied by means of serial bone marrow trephine biopsies (BMB). The BMB were performed during the following stages of the disease: 1 at diagnosis of BT, 2 following ablative therapy and 3 during haematological recovery following autografting. In 10 of the 16 patients, BT was recognized by the presence of a distinctive infiltration with blast cells with a single large hyperchromatic nucleolus. In four of the 16 patients, the diagnosis of BT could only be made by BMB since simultaneous marrow aspiration yielded either a dry tap or no marrow fragments; in two of these four patients the BT was focal in the BMB specimen. Following ablative therapy and during haematological regeneration after autografting, BM aspirates were unsatisfactory in most cases and they were inadequate to assess cellularity or the presence of residual blasts. In contrast, sections of BMB showed clearly whether a decrease in cellularity took place or, in some, residual blasts were still present. BMB samples obtained 2 weeks after autografting showed haemopoietic regeneration consisting of discrete foci of either erythroid, granulocytic or megakaryocytic precursor cells. We conclude that BMB is essential for diagnosing CGL in BT, for monitoring the progress of these patients after therapy and in assessing the haemopoietic regeneration following autografting.
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PMID:Histological study of the bone marrow in chronic granulocytic leukaemia in blast transformation. I. Serial observations before and after autografting. 694 49

In 91 of 106 adult patients with acute lymphoblastic leukemia (ALL) enrolled in the treatment protocol ALL HOVON-5 between May 1988 and October 1991, the immunophenotype of the leukemia was determined and correlated with clinical characteristics at presentation. The immunological marker analysis was performed in ten laboratories, all members of the Dutch Study Group on Immunophenotyping of Leukemias and Lymphomas (SI-HON). Undifferentiated blasts were found in four patients, 67 had B-lineage ALL, 18 had T-lineage ALL, and two had biphenotypic ALL. The age of T-lineage ALL patients was lower (mean 29.3) than that of B-lineage ALL patients (mean 35.5). Tumor mass, as expressed by leukocyte count, organomegaly, and LDH, was more pronounced in T-lineage ALL. Hemoglobin and platelet count was similar in all (sub)types. CD34 was expressed in 58% of the leukemias, but most frequently in the common B-ALL (70%). Thirteen percent of the leukemias expressed one or more markers not associated with their lineage. In this prospective study immunological data were not evaluable for 15 patients. On four of them data were not available because of dry tap, for six patients the typing was technically insufficient, and for four patients the results were unclassifiable; with one patient the marker analysis was not performed.
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PMID:Acute lymphoblastic leukaemia in adults: immunological subtypes and clinical features at presentation. 768 3

A retrospective cohort study was conducted to investigate the relationship between drinking water contamination and risk of leukemia in human being. It was found that the leukemia incidence rate of group D who drank the tap-water from Donghu Lake was significantly higher than that of the groups C and H who drank the tap-water from Changjiang River and Hangjiang River, RR = 1.77, 95% CL = 1.36-2.30, P < 0.01. But the difference between group C and group H is not significant. By using the sex- age-strata analysis; trend and correlation analysis, the results showed that there was a significant positive correlation between the RR of incidence of leukemia and tap-water mutagenicity. It was also connected with pollution of halogenated hydrocarbons in drinking water.
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PMID:[Drinking water and leukemia]. 808 34

We report a successful ereated case of acute megakaryoblastic leukemia (AMKL) with myelofibrosis (MF), which achieved a disease free condition, with disappearance of MF, for over 24 months after allogeneic bone marrow transplantation (BMT) and summarized cases of MF receiving BMT reported in Japan to evaluate the influence of MF on engraftment of bone marrow (BM). A 40-year-old man was admitted on Jan. 29, 1991 due to anemia and thrombocytopenia. BM aspiration resulted in a dry tap and MF and cells stained positive with anti-GPIIb/IIIa (CD41a) antibody were demonstrated by BM the biopsy specimen. Complete remission was achieved by multi-drug chemotherapy including behenoylcytosine arabinoside, etoposide, mitoxantrone and prednisolone (PLS). After preconditioning with little BU+CY, BMT was performed from an HLA-identical brother on Jan. 16, 1992. From day 9 of post BMT, acute skin graft versus host disease (grade 1) was observed, which was controlled by 60 mg/day of PSL. Engraftment was achieved on day 12. Although cystitis developed, he was discharged on Apr. 5, 1992 and remains disease free. Including the present case, seven allogeneic BMT patient with MF have been reported so far in Japan. Four cases in whom MF recovered before BMT showed better results than other three cases that still showed MF at BMT. Reversal of MF seems to be a favorable pre-transplant factor for successful BMT in patients with MF.
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PMID:[Reversal of myelofibrosis is an important pre-transplant factor for bone marrow grafting--a successful case of allogeneic bone marrow transplantation for an acute megakaryoblastic leukemia]. 813 12


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