Molecular Markers in Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a hematopoietic neoplasm characterized by abnormal proliferation of differentiation-arrested primitive myeloid stem cells and progenitors. 1 AML was historically classified according to the French American British (FAB) cooperative group criteria into 8 subtypes (M0-M7) based on the leukemia morphology. 2 The recent World Health Organization (WHO) Classification recognizes the importance of cytogenetic characterization of leukemic cells and categorizes a subgroup of AML patients with recurrent chromosomal aberrations, i.e. AML with t(8;21) (q22;q22), AML with t(15;17)(q22;q21), AML with inv(16)(p13q22)/ t(16;16)(p13;q22), and AML with 11q23 abnormalities into a separate entity. 3 These four entities, however, constitute only 20-30 % of all AML cases in clinical practice. Almost half of the patients do not have any clonal cytogenetic aberrations and this subgroup represents a morphologically heterogeneous group of AML with diploid karyotype. 4 With the advances in the molecular understanding of the mechanism of AML through the identification of molecular genetic changes such as gene mutations and deregulated gene expression, new molecular markers have now emerged. The prognostic effects of these molecular markers on patients ’ ultimate clinical outcome have been shown including mutations in the WT1 gene, MLL gene, FLT3 gene, NPM1 gene, CEBPA gene, KIT gene, and AML1 gene and high expression levels of the BAALC gene, ERG gene, and MN1 gene. 5-6 It is anticipated that a more refined classification based on molecular markers will soon be established to reflect the genetic heterogeneity and diverse leukemogenetic mechanisms in AML. 7 In this review, I will focus on the molecular markers that have been identified in AML patients with normal cytogenetics. The prognostic impact of each molecular marker will be discussed. Classification and risk stratification in AML 1-7 The diagnostic classification of AML has progres-sively evolved in the past 30 years. The FAB Classification (1976), a morphology-based system, has recently bee