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

The association between occupational and other environmental exposures was evaluated in 60 acute myelogenous leukemia cases and controls. Odds ratios and 95% confidence intervals for prior cytotoxic therapy and benzene exposure, adjusted for age, sex, and race by logistic regression, were 3.7 (0.7, 19.9) and 2.6 (0.4, 15.2), respectively. No other work-related associations, including employment in electrical occupations, were present. Other associations were suggestive but may have been due to biases in control selection or small numbers of subjects. The risks for prior cytotoxic therapy (odds ratio = 10.2) and benzene exposure (odds ratio = 11.4) were concentrated in 13 patients with French-American-British M4 leukemia; no environmental exposures were associated with French-American-British subtypes M1 and M2. These findings support the concept that French-American-British histological subtypes of AML may have different etiologies.
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PMID:Is histological subtype a marker for environmental exposures in acute myelogenous leukemia? 130 3

The anti-proliferative effects of selenium were studied both in vivo and in vitro. At a selenium concentration of 0.6 micrograms/ml, cells from patients with ALL-L1, L2 and AML-M1, M3 and M5 were more sensitive than cells from patients with CML. Cells from patients with AML-M2, CLL and leukaemic lymphoma were least sensitive. Normal bone marrow or peripheral blood cells were not sensitive to selenium at this concentration. In the mouse leukaemia models (L797, L615, L7712), the sensitivity of leukaemic cells were: L797 (93% cytotoxicity) greater than L615 (49.7% cytotoxicity) greater than L7712 (4.4% cytotoxicity). Sodium selenite injected i.p. increased the longevity of L797-inoculated mice. Administration of 40 micrograms selenium daily for 7 days resulted in a significant increase in the longevity of mice inoculated with 10(5) L797 cells. However, no remarkable increase of the longevity was observed in either L615- or L7712-inoculated mice after treatment with sodium selenite for 7 days. Treatment of the HL-60 leukaemic cell line with selenium caused a dose- and time-related decrease in DNA, RNA and protein syntheses as measured by [3H]-thymidine, [3H]-uridine and [3H]-leucine uptake respectively. The inhibitory effect of selenium on DNA synthesis was reversed when selenium was removed from the medium, demonstrating that selenium-induced inhibition of DNA synthesis was due to interference with DNA biosynthesis rather than DNA template damage. These results suggest that the anti-leukaemic effect of sodium selenite is associated with inhibition of DNA replication, transcription and translation.
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PMID:The anti-leukaemic effects and the mechanism of sodium selenite. 131 17

Deletions of chromosome 5 were initially reported as a consistently occurring chromosomal abnormality in 5q- syndrome. They have since been recognized to occur in other myeloid malignancies such as therapy-related leukaemia and de novo AML as well. The variability of the deletions, and the heterogeneity of the clinical syndromes, have made it difficult to describe a single clinical-molecular entity such as we see with chromosomal translocations described elsewhere in this volume. Translocations in leukaemogenesis often have a dominant effect leading to activation of oncogenes or the production of a modified protein. Consistently occurring chromosomal deletions in human tumours, however, have been regarded as evidence that the affected regions contain tumour suppressor genes. Loss of function of these tumour suppressor genes or 'recessive oncogenes' leads to cancer. Deletions in the long arm of chromosome 5 in myeloid malignancies are thought to signal the existence of a recessive oncogene on 5q, which is homozygously inactivated in these malignancies. Here we describe the clinical and molecular features of the diseases associated with deletions of chromosome 5 in an attempt to propose a unified approach to identifying the genes on 5q which are involved in leukaemogenesis. It is likely that the clinical heterogeneity of these disorders will not be understood until the relevant genes are cloned and their role in the initiation or progression of leukaemia is known.
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PMID:Myeloid malignancies and chromosome 5 deletions. 133 91

Because neither morphologic nor routine cytochemical features are pathognomonic, the diagnosis of acute megakaryoblastic leukemia (AML-M7) is difficult, requiring either specialized ultrastructural or immunologic techniques. Because the ultrastructural techniques are cumbersome, immunologic assays for expression of several platelet-specific antigens, such as CD41a (platelet glycoprotein IIb/IIIa), have become the primary method used to detect megakaryoblastic differentiation. In our flow cytometric analysis of the immunophenotypes of over 1,000 cases of AML from patients registered to Southwest Oncology Group (SWOG) Treatment Protocols, we found that 38% of cases demonstrated CD41a reactivity. Because this frequency of CD41a expression by flow cytometry greatly exceeded the number of morphologically defined cases of AML-M7, we postulated that the reaction may be caused by platelets adherent to leukemic blasts. To investigate this hypothesis, we performed a side-by-side comparison of flow cytometric and cytospin immunofluorescence studies on 37 cases of adult de novo AML that demonstrated a wide range of CD41a expression by flow cytometric analyses. We found that the expression of CD41a detected by flow cytometric techniques was secondary to adherent platelets or platelet fragments in 85% of cases. Many of these cases also expressed the lineage-specific carbohydrate, LNF III (CD15), which may mediate platelet adhesion to mature monocytes and neutrophils. Only 15% of the CD41a flow cytometrically positive cases demonstrated true diffuse membrane and cytoplasmic positivity on cytospin slides indicative of megakaryoblastic differentiation. Cytospin immunofluorescence for CD41a should be performed on all cases of suspected AML-M7. If only flow cytometric techniques are used, adherent platelets may result in the erroneous diagnosis of this AML subtype.
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PMID:False-positive flow cytometric platelet glycoprotein IIb/IIIa expression in myeloid leukemias secondary to platelet adherence to blasts. 134 44

We analyzed the maintenance of acute myeloid leukemia clonogenic cells (AML CFU-L) in liquid culture in the presence of five potential differentiation inducers: trans-retinoic acid, 1,25-dihydroxy vitamin D3, interferon gamma, granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), used singly and with two combined. The culture medium contained either fetal bovine or human serum from normal donors. CFU-L recovery after 7 days was compared to that observed in control cultures. Of AML cases and HL60 cells, 11/15 displayed greater than 50% CFU-L reduction in response to one or more inducers. In 8/9 responsive cases that underwent the nitroblue tetrazolium (NBT) reduction test, an increase in the percentage of functionally mature (NBT-positive) cells was detected. The combination of retinoic acid with interferon gamma was most effective in reducing CFU-L recovering (8 responsive/15 AML cases), G-CSF and M-CSF displayed either inhibitory or stimulatory activity in different AML cases. The type of serum employed generally did not affect the response to inducers of differentiation. No significant inhibition of the recovery of granulocyte-macrophage colony-forming units was determined by the five inducers in experiments with three normal bone marrow samples. Our experiments indicate that biological differentiation inducers can reduce AML CFU-L self-renewal and increase the proportion of differentiated cells at concentrations that do not affect normal myelopoiesis and could be achieved during treatments in vivo.
Leukemia 1992 Feb
PMID:Self-renewal inhibition of acute myeloid leukemia clonogenic cells by biological inducers of differentiation. 137 69

In an effort to identify unique tyrosine kinases found in human leukemia cell lines, we utilized polymerase chain reaction (PCR) technology and degenerate oligonucleotide primers to produce a cDNA library of kinase catalytic domains found in the human monocytic cell line AML-193. This search yielded a member of the class 3 tyrosine kinases closely related to the murine kinase FD-22. Previous work has identified this kinase as JAK1. This class of tyrosine kinases is characterized by being ubiquitously expressed, lacking both a ligand-binding domain and a SH2 domain, while containing a second domain similar to a degenerate kinase domain. Our studies focused on the further characterization of this class 3 tyrosine kinase using Northern blot analysis to demonstrate an increase in steady-state mRNA by interferon-gamma in human monocytes. A human-hamster somatic cell hybrid panel and linkage mapping was used to assign JAK1 (aml-116) to human chromosome 1.
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PMID:Characterization of a class 3 tyrosine kinase. 137 77

We examined the feasibility of maintaining specific plasma concentrations of ara-C and VP-16 in children with AML. Sixty-one children were treated with 6 sequential cycles of intensive chemotherapy consisting of: (1) cytarabine (ara-C)/VP-16, (2) ara-C/daunorubicin (Dauno), (3) VP-16/amsacrine (m-AMSA), (4) VP-16/5-azacytidine (5-Az), (5) ara-C/Dauno, and (6) ara-C/VP-16. Fifty-nine children had de novo AML, and 2 had a previous myelodysplastic syndrome. The number of patients with each specific FAB subtype was: M0-1; M1-7; M2-24; M3-7; M4-5; M5-11; and M7-6. Simultaneous continuous infusions of ara-C and VP-16 (cycle 1) given at individualized doses to achieve drug plasma concentrations of 1 microM and 30 microM, respectively, produced complete remission (CR) in 26 of 61 patients (43%); an additional 17 patients entered CR after Dauno/ara-C (cycle 2), and one patient required 4 cycles of chemotherapy to achieve CR (total CR rate = 72%). The preliminary 2-year event-free survival (EFS) for patients with FAB-M1 and -M2 AML was only 15% versus 40% for those with FAB-M4 and -M5 AML. Overall, 21 of the 61 patients remain in CR (2-yr EFS = 29%). We conclude that intense treatment with ara-C and VP-16 at doses individualized to achieve target plasma concentrations is feasible although severely myelosuppressive. It results in an acceptable CR rate, but does not improve EFS.(ABSTRACT TRUNCATED AT 250 WORDS)
Leukemia 1992
PMID:Current strategies for treatment of acute myeloid leukemia at St Jude Children's Research Hospital. 137 92

Between 1976 and 1988 we treated 228 children age 18 years or less with AML on three consecutive protocols: Vapa, 80-035 and Hi-C Daze. All three protocols used intensive consolidation chemotherapy. VAPA and 80-035 used an anthracycline with standard dose cytosine arabinoside (ara-c) for remission induction followed by twelve to fourteen months of intensive sequential chemotherapy. Results were similar for these two treatment protocols. 90/125 (72%) of the patients achieved a complete remission with 45% projected disease free survival for the complete responders, and an event free survival of 31%. 8/26 (VAPA) and 3/21 (80-035) relapses were primary CNS. No factor significantly influenced the rate of complete remission, but M4 and M5 FAB subtypes and WBC greater than 100,000/ul predicted for shorter remission duration. 103 children received Hi-C DAZE. The protocol differed by utilizing high-dose ara-c during induction and consolidation and pairing VP-16 with azacytidine. Hi-C DAZE was modified after the first 33 patients (group 1) because of CNS toxicity; VP-16/azacytidine were substituted for high dose ara-c/daunorubicin as the second induction course for the next 70 patients (group 2). Twenty eight of 33 (85%) of group 1 and 54/70 (77%) of group 2 entered remission.
Leukemia 1992
PMID:Intensive sequential chemotherapy for children with acute myelogenous leukemia: VAPA, 80-035, and HI-C-Daze. 137 93

Pretreatment of acute myeloblastic leukemia cells with the hemopoietic growth factor interleukin 3 (IL3) increased their susceptibility to lymphokine activated killing (LAK) but did not affect their constitutive resistance to native natural killer activity. In addition, IL3 treatment did not alter the LAK cell-mediated killing of CD34+ hemopoietic progenitors present in normal bone marrow. Increased 3H-thymidine uptake was generally observed after IL3 treatment. However, failure to proliferate in response to IL3, observed in some cases, did not prevent changes in LAK susceptibility. Enhanced lysis of IL3-treated leukemic cells was accompanied by a moderate increase of the effector-target binding. Increased LAK susceptibility was already observed at 18 h, while optimal cytolysis and expression of the cell adhesion molecule (CAM) LFA-3 (CD58) by IL3-treated AML cells were concomitantly observed at later culture times. In contrast, the CAM ICAM-1 (CD54) was not modulated by IL3, nor were significant changes in the expression of either CAMs observed in normal hemopoietic cells. Blocking experiments with the anti-CD58 monoclonal antibody demonstrated a variable neutralizing effect on the IL3-induced increase of LAK activity, depending on the leukemia cell studied. The effect described here, together with the known role of IL3 in normal hemopoiesis makes it a factor of potential therapeutic value for the treatment of leukemic patients.
Leukemia 1992 Jun
PMID:Effect of human interleukin 3 on the susceptibility of fresh leukemia cells to interleukin-2-induced lymphokine activated killing activity. 137 79

OMA-AML-1 was established from a patient with acute myelomonocytic (M4) leukemia at fifth relapse when blasts were greater than 85% CD34+, CD15-. Leukemic cells were established in suspension culture and independently grown as subcutaneous tumors in SCID mice. Cells growing in suspension culture underwent differentiation by phenotypic and morphologic criteria. In contrast, cells grown as subcutaneous solid tumors in SCID mice maintained progenitor cell characteristics with high-density CD34 expression and lack of morphologic differentiation. A tendency toward differentiation to CD15+, CD34- cells in vitro and self-renewal of CD34+, CD15- cells in vivo was consistently demonstrated regardless of whether cells were initially grown in vitro or in vivo. The cell line maintains both a CD34+, CD15- progentitor cell pool and a non-overlapping, CD15+, CD34- differentiating cell compartment after more than 1 year in continuous culture. Cell cycle analysis and cloning experiments were consistent with terminal differentiation occurring in the CD15+, CD34- population. The cell line shows concentration-dependent proliferative responses to interleukin (IL)-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-6, but not to granulocyte CSF (G-CSF). OMA-AML-1 appears to mimic several features of normal myeloid hematopoiesis and should prove useful for the study of normal and malignant myeloid differentiation.
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PMID:OMA-AML-1: a leukemic myeloid cell line with CD34+ progenitor and CD15+ spontaneously differentiating cell compartments. 137 48


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