Is There an Entity of Chemically Induced BCR-ABL–Positive Chronic Myelogenous Leukemia?

Abstract

Abstract Learning Objectives After completing this course, the reader will be able to: Distinguish the exogenous causes of acute and chronic myelogenous leukemia.Discuss the evidence establishing the exogenous causes of secondary leukemia.Describe the relationship of radiation and chemical exposure to the risk of developing specific subtypes of leukemia. CME This article is available for continuing medical education credit at CME.TheOncologist.com Advances in the therapy of malignancy have been accompanied by an increased frequency of cases of secondary acute myelogenous leukemia and related clonal cytopenias and oligoblastic (subacute) myelogenous leukemia (myelodysplastic syndromes). The acute myelogenous leukemia incidence can be increased by high-dose acute ionizing radiation exposure, alkylating agents, topoisomerase II inhibitors, possibly other DNA-damaging therapeutic agents, heavy, prolonged cigarette smoking, and high dose-time exposure to benzene, the latter less frequently seen in industrialized countries with worksite regulations. Acute myelogenous leukemia and myelodysplastic syndromes may result from innumerable primary types of chromosome damage. In the case of chronic myelogenous leukemia, a specific break in chromosome bands 9q34 and 22q11 must occur to result in the causal fusion oncogene (BCR-ABL). A review of 11 studies of the chromosomal abnormalities found in presumptive cases of cytotoxic therapy–induced leukemia and of 40 studies of the subtypes of leukemia that occur following cytotoxic therapy for other cancers has not provided evidence of an increased risk for chemically induced BCR-ABL–positive chronic myelogenous leukemia. Studies of the effects of alkylating agents, topoisomerase inhibitors, and benzene on chromosomes of hematopoietic cells in vitro, coupled with the aforementioned epidemiological studies of secondary leukemia after cytotoxic therapy or of persons exposed to high dose-time concentrations of benzene in the workplace, do not indicate a relationship among chemical exposure, injury to chromosome bands 9q34 and 22q11, and an increased risk for BCR-ABL–positive chronic myelogenous leukemia.