© 1996 by Oxford University Press
Journal of the National Cancer Institute, Vol. 88, No. 7, 407-418,
April 3, 1996
© 1996 Oxford University Press
The Secondary Leukemias: Challenges and Research Directions
Clinical Trials Evaluation Program, Division of Cancer Treatment, Diagnosis, and Centers National Cancer Institute Bethesda, MD
Chemoprevention Branch, Division of Cancer Prevention and Control, National Cancer Institute Bethesda, MD
Section of Medical Oncology, Evans Department of Clinical Research, Boston University Medical Center MA
Correspondence to: Judith E. Karp, M.D., National Institutes of Health, Executive Plaza North, Rm. 212C, Bethesda, MD 20892.
Acute myelogenous leukemia (AML) arising following exposure to genotoxic agents has been recognized as a distinctive entity for more than 40 years. Secondary, or therapy-related, AML accounts for 10%–20% of all AML cases. This review addresses four overarching areas of investigation focused on secondary AMLs: 1) dissection of the molecular structure of the induced genetic lesions and identification of the functional consequences of these changes, thereby providing clues to the pathogenesis of secondary AML and potentially serving as a basis for innovative therapeutic interventions; 2) identification and characterization of mechanisms of DNA damage and the orderly repair of such damage; 3) identification and application of accurate biomarkers of leukemogenesis for the purpose of risk prediction and quantification, potentially allowing recognition of patients especially susceptible to the leukemogenic effects of chemotherapy (for genetic or acquired reasons) and allowing their treatment for cancer to be modified on the basis of this susceptibility; and 4) design and implementation of longitudinal clinical and genetic monitoring of high-risk populations (i.e., individuals undergoing cytotoxic therapies for primary cancers). This review of the literature relating to these areas builds upon these themes and attempts to synthesize these seemingly disparate areas of research so that they can be more effectively utilized together to address the problem of secondary AML. Ultimately, the evaluation of these areas will improve our understanding of de novo leukemia and will serve as a springboard for the development of new concepts of therapy and prevention. [J Natl Cancer Inst 1996;88:407–18]
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