Chromosome Banding Studies in Acute Leukaemia at Diagnosis

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A case report of serial chromosome studies on a child presumed to have acute lymphoblastic leukemia (ALL) is presented. Hematologic remission was achieved after 3 weeks and maintained until death 63 weeks later. The classic Philadelphia chromosome translocation was found, both at diagnosis and throughout the course of the disease, in a proportion of cells from PHA-stimulated blood cultures. The finding is related to other reports of Philadelphia-positive clones in ALL, as well as those in chronic myeloid leukemia and its acute transformation, and other myeloproliferative disorders. The origin of the Philadelphia chromosome in this case is considered in the light of current stem cell theory, and its relevance to lymphocytic neoplasia is discussed. We believe that the finding of a Ph1-positive clone in a cell line morphologically indistinguishable from normal lymphocytes in a case of acute leukemia is unique.

Philadelphia chromosome in acute leukemia.Case report

Walker

Hardy

1976

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Chromosomes and causation of human cancer and leukemia.XXVI. Banding studies in acute lymphoblastic leukemia (ALL)

Oshimura

Freeman

Sandberg

1977

176

Chromosomes were studied in the bone marrow cells of 101 patients with acute lymphoblastic leukemia (ALL) hospitalized at or attending the clinics of Roswell Park Memorial Institute (RPMI) between January, 1968, and December, 1976. Aneuploidy was observed in about 50% (54/101) of the cases. Two cases were hypodiploid and the remaining were either pseudo or hyperdiploid. The frequency of abnormalities and the chromosomal numbers were similar to those of 106 cases studied in our laboratory prior to 1968. Of 50 recently unselected cases of ALL in whom Q-and G-banded karyotypes were attempted, 31 were successfully analyzed with these techniques. The banding patterns revealed 16 cases to have chromosome abnormalities and four of these to have a similar abnormality, i.e., partial deletion of the long arm of chromosome #6: two cases had a 6q-with additional abnormalities and two had 6q-as the sole karyotypic abnormality. The breakpoint in chromosome #6 seemed to involve a segment from q21 to q25. An isochromosome of the long arm of #7, i(7q), was observed in two cases, two additional #21 chromosomes were observed in five cases and, except for the Y, all other chromosomes participated in the karyotypic changes encountered in the 16 cases in which banding analyses were performed. Banding analysis has afforded the first reliable approach towards ascertaining karyotypic evolution in ALL, which was achieved in eight cases of the present study. The chromosomes contributing to this karyotypic evolution were distributed widely. Thus, all chromosomes except the Y participated in numerical and/or structural karyotypic changes. Even though nonrandom chromosome changes may occur early in ALL, the pristine prototypic picture of the karyotypes in ALL is often obfuscated by successive chromosomal changes and hyperdiploidy by the time the karyotypes are analyzed in this condition. Further cytogenetic studies are required, with special attention to karyotypic evolution, in order to uncover the significance of chromosomal changes in early and late ALL.

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

Cadman

Capizzi

Bertino

1977

204

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).