The term acute myeloid leukemia (AML) is used to describe several neoplastic blood disorders characterized by clonal expansion of immature myeloid cells in the bone marrow (BM), blood, or other tissue,12 as a result of increased cell proliferation, prolonged survival, and/or disruption of differentiation of hematopoietic progenitor cells. Although the etiology of AML is still unknown, the risk of developing AML is increased by exposure to ionizing radiation and chemical mutagens such as alkylating agents, benzene, and topoisomerase II inhibitors. The risk of AML is also considerably greater in patients suffering from Down syndrome and rare genetic disorders such as Bloom syndrome, neurofibromatosis, Schwachman syndrome, ataxia-telangiectasia, Klinefelter syndrome, Fanconi anemia, and Kostmann granulocytic leukemia.3 The aforementioned associations suggest a role of genetic factors in initiating leukemogenesis. Indeed, advances in basic and clinical research have revealed that malignant transformation in all patients with AML, the vast majority of whom do not suffer from inherited genetic disorders, is associated with acquisition of somatic mutations and/or epigenetic events, such as hypermethylation, that affect and change expression of genes involved in hematopoiesis.

Many AML-associated genetic rearrangements can be detected cytogenetically as nonrandom chromosome abnormalities, while others are submicroscopic and detectable only by molecular genetic techniques [e.g., a reverse transcription polymerase chain reaction (RT-PCR)].4-6 A single genetic abnormality is usually not sufficient to cause overt leukemia, but multiple alterations of different pathways within the same cell are involved in the process of leukemogenesis. It appears that at least two different kinds of mutations must occur in the hematopoietic progenitor cell to transform it into a malignant cell, initiating development of a clonal AML blast population. These are (1) mutations that activate genes involved in signal trans-duction of proliferation pathways and thereby confer a survival advantage and increase the rate of cell proliferation (referred to as "class I mutations"), and (2) mutations of genes encoding hematopoietic transcription factors, in the form of either gene fusions generated by reciprocal chromosome translocations or intragenic mutations, which disrupt the process of normal cell differentiation ("class II mutations").7

A number of cytogenetic and molecular genetic rearrangements correlate well with the morphology and/or immunophenotype of leukemic marrow and blood, as well as the patients' clinical characteristics, and are therefore incorporated into the World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues.1 In other instances, such correlations are less clear, and subtypes of AML are identified primarily on the basis of morphological and cytochemical criteria. In this chapter, we will review major types of AML with an emphasis on cytogenetic and molecular genetic findings.

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