Association of a Leukemic Stem Cell Gene Expression Signature With Clinical Outcomes in Acute Myeloid Leukemia

Abstract

Acute myeloid leukemia (AML) is an aggressive malignancy of the bone marrow characterized by accumulation of early myeloid blood cells that fail to mature and differentiate. The course of the disease is marked by poor prognosis, frequent relapse, and high disease–related mortality.^1,2 Recent clinical investigation has focused on the identification of prognostic subgroups in adult AML with the goal of guiding patients into risk-adapted therapies. Such investigation determined that cytogenetic abnormalities are prognostic, some favorable and others unfavorable,^3,4 yet up to 50% of patients have normal karyotype AML with a wide range of clinical outcomes. In these patients, the presence of specific molecular mutations can provide prognostic information, including internal tandem duplications within the FLT3 gene, partial tandem duplication of the MLL gene, mislocalizing mutations of the NPM1 gene, mutations in the CEBPA and RAS genes, and increased expression of the BAALC and ERG genes.^5,6 However, these parameters and others such as patient age are only partially successful at capturing risk of relapse and patient outcomes following treatment.