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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.