Acute myelogenous leukemia (AML) is a group of several different diseases, the treatment and outcome of which are dependent on several factors including leukemia karyotype, patient age, and comorbid conditions. Despite advances in understanding the molecular biology of AML, its treatment remains challenging. Standard regimens using cytarabine and anthracyclines for induction followed by some form of postremission therapy produce response rates of 60% and 5-year survival rates of 25%. New therapies are emerging based on the definition of specific cytogenetic-molecular abnormalities. Such targeted therapies offer the promise of better antileukemic activity in adult AML.
Acute leukemias are clonal malignant hematopoietic disorders, resulting from genetic alterations in normal hematopoietic stem cells. These alterations induce differentiation arrest and/or excessive proliferation of abnormal "leukemic" cells or "blasts."
Acute myelogenous leukemia (AML; acute nonlymphocytic leukemia) is heterogeneous. Over the past several decades, improvements in chemotherapeutic regimens and supportive care have resulted in significant but modest progress in treating AML. Better understanding of the biology of AML has resulted in the identification of new therapeutic targets. Despite current optimism, most patients with AML still die of their disease. With better molecular definition and elucidation of the physiopathology of AML subtypes, and development of new and targeted therapies, a better outcome of AML may be achievable in the future.
About 13,000 individuals are diagnosed annually in the United States with AML. The incidence of AML is 2.7 per 100,000 (1,2). The median age at presentation is about 65 years. The incidence of AML, along with its precursor, myelodysplasia, appears to be rising, particularly in the population over age 60. In adults, AML is by far the most common type of acute leukemia. The incidence of AML is slightly higher in males and in populations of European descent. Acute promyelocytic leukemia (APL), a distinct subtype of AML, is more common among populations of Latino or Hispanic background (3,4).
An increased incidence of AML is seen in patients with disorders associated with excessive chromatin fragility such as Bloom syndrome, Fanconi anemia, Kostmann syndrome, and with Wiskott–Aldrich syndrome or ataxia–telangiectasia. Other syndromes such as Down (trisomy of chromosome 21), Klinefelter (XXY and variants), and Patau (trisomy of chromosome 13) have also been associated with a higher incidence of AML (5–8).
Survivors of the atomic bombs in Japan had an increased incidence of myeloid leukemias that peaked 5 to 7 years following exposure (7). Therapeutic radiation increases AML risk, particularly if given with alkylating agents. There are two main types of therapy-related AML. The "classic" alkylating-agent type (eg, cyclophosphamide, melphalan, nitrogen mustard) has a latency period of 4 to 8 years, and is often associated with abnormalities of chromosomes 5 and/or 7. Exposure to agents that inhibit the DNA repair enzyme topoisomerase II (eg, etoposide, teniposide) is associated with secondary AML with a shorter latency period, usually 1 to 3 ...