Emerging Therapies in Cytogenetically Normal Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML) is a clinically and biologically heterogeneous clonal disorder of hematopoietic progenitor cells that results in disturbed cellular growth, proliferation, and differentiation. Since the first published description of leukemia in 1827, continued advances in molecular biology have been paramount in deciphering the pathogenesis of disease. In AML, somatic mutations are often thought to contribute to leukemogenesis. Genetic variation in AML is measured using molecular karyotyping and has become the most important tool for risk stratification and defining prognosis. However, in approximately 40-50% of AML patients, no clonal chromosomal aberrations are detected. Such cases of cytogenetically normal AML (CN-AML) are currently categorized in the intermediate risk group, though much heterogeneity remains present within this group. Gene profiling by DNA analysis has further conferred prognostic significance in adult patients with CN-AML. The expansion of knowledge on the effects of genetic variation has provided new opportunities to develop a more personalized approach and tailoring treatment based on genetic characteristics. This review describes important genetic characteristics of CNAML, and provides an overview of the therapeutic agents that are currently being investigated in the treatment of this disorder.