Development Of Acute Nonlymphocytic Leukemia Research Articles

Spatially restricted expression of set mRNA in developing rat kidney.

A somatic translocation event fusing the novel gene set to the putative oncogene can has been implicated in the development of acute nonlymphocytic leukemia in humans. In this study, full-length cDNAs highly homologous with human set were cloned from a rat neonatal kidney library. The expression pattern of set mRNA was then examined in developing rat kidney. Two groups of set cDNAs (alpha and beta) with different translation initiation sites and open reading frames of 867 and 831 bp, respectively, were found. The predicted protein products are 33,385 and 32,085 Da in size and contain approximately 30% acidic residues, over half of them clustered at the COOH terminal, thus forming a long acidic tail. No signal peptide or membrane-spanning domains were identified, suggesting an intracellular protein product. By ribonuclease protection assay, both alpha and beta variants of set were expressed in kidney. On Northern blots of total kidney RNA, 3.0- and 2.2-kb mRNAs hybridized with the labeled set cDNA probe. Expression of both transcripts was four- to eightfold greater in neonatal compared with adult rat kidney. When neonatal rat kidneys were examined for set mRNA expression by in situ hybridization with 35S-labeled riboprobe, expression was densely localized in the cortical region of morphogenesis over primitive nephron structures, including S-shaped bodies. Thus mRNA for Set, a putative intracellular protein involved in leukemogenesis, is expressed in kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Cigarette smoking, leukemia, and multiple myeloma

To evaluate previously reported associations with cigarette smoking, the incidence of leukemia and multiple myeloma was determined with follow-up of up to 24 years of 57,224 never-smokers, 20,928 former smokers, and 64,839 current cigarette smokers who received multiphasic health checkups. Cigarette smoking was associated with the development of acute nonlymphocytic leukemia in men only (relative risk, 2.8; 95% confidence interval, 1.2 to 6.4). Chronic myeloid leukemia showed an association with smoking of borderline significance in men only. Chronic lymphocytic leukemia and multiple myeloma were not related to cigarette smoking. In the men with acute nonlymphocytic leukemia there was a suggestion of a dose-response relation but it was not statistically significant. The association of cigarette smoking with acute nonlymphocytic leukemia was not explained by alcohol or coffee consumption or exposure to occupational hazards. This study adds to the growing body of evidence that cigarette smoking predisposes to acute nonlymphocytic leukemia in men.

Relationship Between Acute Myelomonoblastic Leukemia and Infection Due to Human Immunodeficiency Virus

Infection due to the human immunodeficiency virus (HIV) has been complicated by the development of acute nonlymphocytic leukemia in five patients whose cases have previously been reported; other manifestations, including preleukemia, myelofibrosis, and myeloid hyperplasia, have also been reported in patients infected with HIV. We report the sixth case of an HIV-infected patient who developed acute myelomonocytic leukemia; HIV infection was documented by tests for serum antibodies (enzyme-linked immunosorbent assay and western blotting), by a markedly elevated p24 antigen level in plasma, and by cultures of CSF and peripheral blood that were positive for HIV. Furthermore, myelomonoblasts that were cultured without the addition of growth factors displayed evidence of HIV replication through the presence of p24 antigen and reverse transcriptase activity, both of which lasted for 4 weeks in the supernatant fluid of the cell cultures. This case report provides the first data indicating that HIV may infect myelomonoblasts in vivo and represents the sixth reported case of an association between HIV infection and pure acute nonlymphocytic leukemia.

Subsequent development of acute non-lymphocytic leukemia in patients treated for Hodgkin's disease.

A nested case control study was carried out to investigate the association between treatment of patients with Hodgkin's disease (HD) and the risk of developing acute non-lymphocytic leukemia (ANLL). Seven Cancer Centers of the International Cancer Patient Data Exchange System of the UICC participated. A study cohort was selected consisting of 1,681 nonpretreated patients with HD, diagnosed from 1972 through 1978, and followed up through 1984. The median follow-up time was 66 months. Eighteen cases of leukemia were observed in the cohort. The risk of development of ANLL was significantly greater for male than for female patients. The treatment characteristics associated with an increased risk of developing ANLL were extensive radiotherapy, splenectomy and the chemotherapy combination of vincristine, procarbazine and mechlorethamine.

Incidence of neoplasms in patients with rheumatoid arthritis exposed to different treatment regimens

Immunosuppressive drugs have been used during the last 30 years in treatment of patients with severe rheumatoid arthritis. The drugs commonly used are cyclophosphamide and chlorambucil (alkylating agents), azathioprine (purine analogue), and methotrexate (folic acid analogue). There is evidence that all four immunosuppressive drugs can reduce synovitis, but disease activity almost always recurs after therapy is stopped. Since adverse reactions are frequent, less than 50 percent of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months to achieve maximal effects, those patients who are unable to continue the drug receive little benefit from it. Patients treated with alkylating agents have an increased risk of development of acute nonlymphocytic leukemia, and both alkylating agents and azathioprine are associated with the development of non-Hodgkin's lymphoma. Cyclophosphamide therapy increases the risk of carcinoma of the bladder. There have been several long-term studies of patients with rheumatoid arthritis treated with azathioprine and cyclophosphamide and the incidence of most of the common cancers is not increased. Data on the possible increased risk of malignancy in rheumatoid arthritis are still being collected, and until further information is available, the use of immunosuppressive drugs, particularly alkylating agents, in the treatment of rheumatoid arthritis should be reserved for patients with severe progressive disease or life-threatening complications.

Lymphocyte abnormalities in preleukemia — I. Decreased NK activity, anomalous immunoregulatory cell subsets and deficient EBV receptors

The development of acute non-lymphocytic leukemia is preceded by a set of symptoms described as the preleukemia syndrome. Six patients who fulfilled the criteria for this preleukemia syndrome have been evaluated for abnormalities in the lymphocyte population. The NK cell activity was reduced, the immunoregulatory cell populations were numerically abnormal, and the B cell subpopulation was deficient in EBV receptors. Thus, in addition to the abnormalities in the myeloid populations, there are serious defects in the lymphoid systems of preleukemic patients.

The preleukemic syndromes (hematopoietic dysplasia) in childhood.

The preleukemic syndrome or hematopoietic dysplasia is a marrow stem-cell disorder with clinically recognizable hematologic abnormalities which precede the development of acute nonlymphocytic leukemia. Its occurrence in childhood is extremely rare; seven "true" cases who fulfill all the criteria for the disorder have been reported until now. The preleukemic syndrome is generally characterized by peripheral cytopenia with fairly specific morphologic abnormalities in cell differentiation. The hematological and clinical features permit recognition of preleukemia even before the development of overt leukemia. Experimental data indicate that preleukemia is an "early" leukemic syndrome in which hematopoietic cell differentiation becomes progressively impaired with termination in the nearly complete maturation block which is characteristic of acute myelogenous leukemia.

Acute nonlymphocytic leukemia.A delayed complication of Hodgkin's disease therapy: Analysis of 109 cases

The use of combined modality therapy (irradiation and combinations of drugs) in the treatment of Hodgkin's disease has produced a significant improvement in survival, during which most patients lead an active and productive life. The estimated 1% incidence of leukemia in treated Hodgkin's disease patients, however, is greater than would be expected in the general population. There is a vast amount of literature which indicates that alkylating agents, procarbazine and irradiation are leukemogenic and immunosuppressive in animals and man. It is than conceivable that the current intensive treatment programs which use these agents are promoting the development of acute non-lymphocytic leukemia (ANLL). This leukemia has occurred most often in patients whose Hodgkin's disease is poorly controlled and who have received more aggressive therapy. The latent period from the diagnosis of Hodgkin's disease to the diagnosis of leukemia is significantly shorter (p less than .0005) in those patients who have received intensive and near maximal radiotherapy (total nodal irradiation), combination chemotherapy (MOPP or equivalent) or a sequential combination of the two modalities than similar patients who were treated with less than total nodal irradiation and or single agent chemotherapy. The following characteristic features have occurred with sufficient frequency to suggest that the subsequent leukemia is a distinct clinicopathological entity: pancytopenia, megaloblastoid marrow, nucleated red blood cells in the peripheral blood, random chromosomal aberrations of the bone marrow in most patients (94%), and refractoriness to antileukemia therapy (response rate 6.5%) with a very short survival (median one month).