Acute nonlymphocytic leukemia in adults: pathophysiology, status of current therapy, and new approaches.

Abstract

Recent information concerning the cell biology of leukemias has provided new insights into the pathophysiology and pathogenesis of acute leukemia, involving the detection of leukemia viruses, oncogenes and their products, and the discovery of factors supporting clonal leukemic growth. Murine, avian, and cat leukemia viruses are well characterized. To date, only HTLV I appears to be a likely candidate as a human leukemia virus. For both avian and murine viruses, there is a fundamental classification distinction between long-latency viruses (LLV) and acute transforming viruses (ATV). The ATV are replication defective and must be propagated with a helper virus. They have within their genome an identifiable oncogene. The LLV do not contain such an oncogene and presumably act by “promotor insertion”, e.g., a retroviral long terminal repeat (LTR inserted 5’ to the cellular oncogene. Acutely appearing neoplasms are probably not clonal, but reflect infection of multiple target cells. Long-latency neoplasms, however, are clonal and probably reflect expansion of a random oncogenic event. There are usually differences between in vitro and in vivo target cell specificities for these viruses. Furthermore, pathogenicity in the animal is greatly affected by animal age, inoculum route, and the genetics of the recipients. Target cell specificities will hopefully be classified by new in vitro culture techniques for hematopoietic cells. Three avian ATV are interesting because of their apparent target cell specificity:AEV (erythroblastosis virus), AMV (myeloblastosis virus), and MC 29 (myelocytomatosis virus). Relative numbers of target cells appear to differ for these viruses: 50 for AEV, 700 for AMV, and 3500 for MC 29. AEV (V-erb B) affects erythroid precursors (presumably BFU-E), AMV (Vmyb), early myeloid precursors, and MC 29 (V-myc), macrophage-like cells. In vitro AEV and MC 29, but not AMV, transform fibroblasts.KeywordsAcute Myeloid LeukemiaHairy Cell LeukemiaCytosine ArabinosideAcute Myeloblastic LeukemiaErythroblastosis VirusThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.