Advances in understanding the biology and genetics of acute myelocytic leukemia

Acute myelocytic leukemia (AML) is a malignant neoplasm of hematopoietic cells characterized by an abnormal proliferation of myeloid precursor cells, decreased rate of self-destruction and an arrest in cellular differentiation. The leukemic cells have an abnormal survival advantage. Thus, the bone marrow and peripheral blood are characterized by leukocytosis with a predominance of immature cells, primarily blasts. As the immature cells accumulate in the bone marrow, they replace the normal myelocytic cells, megakaryocytes, and erythrocytic cells. This leads to a loss of normal bone marrow function and associated complications of bleeding, anemia, and infection. The incidence of AML increases with age, peaking in the sixth decade of life. In the United States, there are about 10,000 new cases of AML and 7,000 deaths in those with an AML diagnosis per year. Current molecular studies of AML demonstrate that it is a heterogeneous disorder of the myeloid cell lineage. This paper will discuss the most recent understanding and research of the cellular origin of AML and associated common genetic mutations that fuel the neoplastic process. Also discussed are how these advances have impacted the classification, selection of therapy, and definition of complete remission in AML. Promyelocytic leukemia will be discussed in detail as this AML subtype reveals how our understanding of the biology and genetics of the disease has led to targeted therapy that results in a cure in up to 80% of patients.