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Molecular genetics of acute myeloid leukemia

Wendy Stock, MD
Michael J Thirman, MD
Section Editor
Richard A Larson, MD
Deputy Editor
Alan G Rosmarin, MD


Acute myeloid leukemia (AML) develops as the consequence of a series of genetic changes in a hematopoietic precursor cell. These changes alter normal hematopoietic growth and differentiation, resulting in an accumulation of large numbers of abnormal, immature myeloid cells in the bone marrow and peripheral blood. These cells are capable of dividing and proliferating, but cannot differentiate into mature hematopoietic cells (ie, neutrophils).

Similar to other malignancies, the genetic alterations in AML include mutation of oncogenes as well as the loss of tumor suppressor genes. In contrast to most solid tumors, many hematologic malignancies are associated with a single characteristic cytogenetic abnormality (eg, the Philadelphia chromosome [t(9;22)] in chronic myeloid leukemia and t(15;17) in acute promyelocytic leukemia).

Advances in the identification of recurring chromosomal abnormalities and translocations have provided major insight into the pathobiology of AML. (See "Tools for genetics and genomics: Cytogenetics and molecular genetics".)

Specific cytogenetic abnormalities identified by karyotype analysis have considerable prognostic significance for patients with AML and affect treatment planning (table 1). Abnormalities in certain genes (eg, mutations in FLT3, nucleophosmin, KIT) as well as gene expression profiles confer prognostic significance in adult patients with AML. Even those patients without obvious abnormalities detected by karyotypic analysis or gene expression profiles have acquired copy number alterations that may help to identify genes important for the pathogenesis of AML [1,2]. (See "Prognosis of acute myeloid leukemia".)

The focus of this topic review will be on the various molecular genetic events involved in the pathogenesis of AML. More general discussions of genetic events in hematologic malignancies are presented separately. (See "Genetic abnormalities in hematologic and lymphoid malignancies" and "General aspects of cytogenetic analysis in hematologic malignancies".)


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