Leukemia (2008) 22, 915–931; doi:10.1038/leu.2008.19; published online 21 February 2008

Cooperating gene mutations in acute myeloid leukemia: a review of the literature

A Renneville1,4, C Roumier1,4, V Biggio1, O Nibourel1, N Boissel2, P Fenaux3 and C Preudhomme1

Acute myeloid leukemia (AML) is a heterogeneous group of neoplastic disorders with great variability in

clinical course and response to therapy, as well as in the genetic and molecular basis of the pathology.

Major advances in the understanding of leukemogenesishave been made by the characterization and the

study of acquired cytogenetic abnormalities, particularly reciprocal translocations observed in AML.

Besides these major cytogenetic abnormalities, gene mutations also constitute key events in AML

pathogenesis. In this review, we describe the contribution of known gene mutations to the understanding

of AML pathogenesis and their clinical significance. To gain more insight in this understanding, we

clustered these alterations in three groups: (1) mutations affecting genes that contribute to cell

proliferation (FLT3, c-KIT, RAS, protein tyrosine standard phosphatase nonreceptor 11); (2) mutations

affecting genes involved in myeloid differentiation (AML1 and CEBPA) and (3) mutations affecting genes

implicated in cell cycle regulation or apoptosis (P53, NPM1). This nonexhaustive review aims to show how

gene mutations interact with each other, how they contribute to refine prognosis and how they can be

useful for risk-adapted therapeutic management of AML patients.