Banded bone marrow chromosome analyses have been done on 83 unselected patients with acute lymphoblastic leukemia (ALL). Seven patients, all with non-T, non-B ALL, had a translocation involving the long arms of chromosomes 4 and 11. Five of these patients, 4 children and 1 adult, were first studied at diagnosis, and the t(4;11) (q21;q23) was the only karyotypic abnormality. All 5 presented with a marked leukocytosis (greater than 150 X 10(9)/liter). Four of these 5 patients achieved a complete remission following the same intensive treatment regimen; however, remission duration and survival were very short (medians 2.5 and 8 mo, respectively). The fifth patient is currently receiving induction chemotherapy. The remaining 2 patients, both adults, were studied in relapse only, and had other karyotypic abnormalities in addition to the t(4;11). One of these relapse patients was a female whose clinical presentation and course were similar to those above. The last patient was a male who presented with a leukocyte count of 7 X 10(9)/liter and maintained an initial complete remission for 37 mo. Our data suggest that patients who have a t(4;11) (q21;q23) at the time of diagnosis of ALL have a poor prognosis with conventional therapy and require a new therapeutic approach.
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[Show abstract][Hide abstract] ABSTRACT: The chromosome Hq23 band Â¡s a genetic region frequently involved in nonrandom karyotypic abnormalities of acute leukemia. A genomic locus named ALL-1 or I//./., where Hq23 breakpoints are clustered, has been recently cloned and characterized. We have made use of an Â¿Â¿Â¿-/-specific probe in Southern blot experiments to analyze the configuration of this gene in a large series of acute leukemia patients, representative of all different myeloid and lymphoid subtypes. Nine of 145 cases (6.2%) showed abnormal ALL-1 restriction fragments in leukemic DNAs. Of these nine cases. Five patients in whom karyotypic data were available displayed chromosome Ilq23 aberrations, including t(4;ll) (three cases) and t(9;ll) (two cases). Immunophenotypic and mor- phocytochemical characterization of Â¿Â¿Â¿-/-rearranged acute leukemia revealed prevalence of poorly differentiated B lymphoid and/or monoblas- tic features. Considering the whole series, ALL-1 rearrangements were significantly associated with female sex, higher white blood cell counts at presentation, and very poor clinical outcome. The presence of residual disease was molecularly documented in one case at the time of clinical remission after induction treatment and was followed by early relapse. We conclude that ALL-1 rearrangements are new molecular markers of hu man leukemia with considerable diagnostic and prognostic relevance.
[Show abstract][Hide abstract] ABSTRACT: Immunologic classification based on lymphocyte surface markers of the leukemic cells has been widely applied in childhood acute lymphoblastic leukemia [1–3]. Multiple studies suggest the clinical importance of such classification. However, relatively little data are available regarding immunologic classification of adult ALL. This article summarizes current knowledge regarding the clinical utility of classifying adult ALL according to the immunologie phenotype of the neoplastic cell as defined by surface markers. The major immunologie classes that have been identified in adult ALL are first described. The biological and clinical characteristics of the major immunologie classes are then presented. Finally, the therapeutic and prognostic implications of these classes are considered. The data in this article come from three major sources: the published literature, the University of Minnesota series, and the Third International Workshop on Chromosomes in Leukemia.