Translational Studies in Elderly Patients with Acute Myeloid Leukemia

The production of blood cells (hematopoiesis) takes place in the bone marrow. Acute myeloid leukemia (AML) is a clonal disease, which is characterized by an increase in the number of myeloid cells in the bone marrow and an arrest in their maturation. This frequently results in a severe suppression of normal hematopoiesis (granulocytopenia, anemia and/or thrombocytopenia).1,2 AML is a heterogeneous disease, characterized by a diversity of morphologic, cytogenetic and immunophenotypic features. Until recently, the morphologic classification was according to the French-American-British group,3-5 which distinguishes AML into nine distinct subtypes (FAB M0-M7, M4eo) that differ with respect to the particular myeloid lineage involved and the degree of leukemic-cell differentiation. This distinction is based on the morphologic appearance of the blasts and their reactivity with histochemical stains. In addition, immunologic methods have been incorporated into the diagnostic criteria for some FABgroups, e.g. M0 and M7.6,7 Cytogenetic abnormalities of the chromosomes in the leukemic blasts have also been shown to be associated with specific FAB subtypes, e.g. t(15;17) with acute promyelocytic leukemia (APL; AML M3).8 Recently, the World Health Organization (WHO) has proposed a new classification for myeloid neoplasms.9 In this classification, genetic features (cytogenetic and molecular genetic) and clinical features have been integrated with morphology and immunophenotype to define distinct disease entities. Within the category of AML, four main groups have been recognized: 1. AML with recurrent cytogenetic translocations; 2. AML with myelodysplasia-related features; 3. therapy-related AML and MDS; and 4. AML not otherwise specified.