Acute Myeloid Leukemia (AML)

Overview
  • Acute Myeloid Leukemia (AML) is a neoplasia of the early myeloid precursor, termed the "myeloblast". Like all acute leukemias, AML follows a rapid course and clinical consequences are largely the result of marrow infiltration. In general, AML is a disease of the elderly and can be rapidly fatal if not treated.
Pathogenesis
  • AML is caused by neoplastic transformation of myeloblasts, an early progenitor of myeloid cells in the normal sequence of hematopoiesis. Like all acute leukemias, neoplastic cells initially proliferate in the bone marrow and can then spill out into the peripheral blood and solid lymphoid organs such as the spleen, lymph nodes, and liver.
Morphology
  • AML "blasts" share common features with those of all acute leukemias, visible as large cells with large nuclei that possess a fine granular cytoplasm and nucleoli. Unique features of AML "blasts" are the presence of granules within the cytoplasm, a reminder of their myeloid heritage. One defining morphological feature of AML blasts is the presence of cytoplasmic needle-like structures, termed "Auer Rods", that represent fusions of individual granules.
Subtypes
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  • A sizable number of AML subtypes exist, defined morphologically and cytogenetically by a French-American-British (FAB) classification scheme into M1-M7 subtypes. These subtypes represent neoplastic cells that show slight differentiation toward one of the myeloid subtypes. A detailed understanding of these subtypes is not necessary except for the M3 subtype which is referred to as "Acute Promyelocytic Leukemia" (APL)
  • APL is characterized by a unique cytogenetic profile, carrying the t(15;17) translocation. This particular translocation between Chromosome 15 and Chromosome 17 causes a fusion of the PML gene with the RAR-alpha gene, the steroid hormone receptor for Vitamin A. The unique feature of the APL subtype is that treatment of patients with All-trans Retinoic Acid (ATRA), a Vitamin A derivative, can induce differentiation of neoplastic cells down the myeloid line toward neutrophils, rendering them re-mortalized and thus non-neoplastic. ATRA therapy is now standard for the APL subtype; however, in most cases patients will ultimately relapse and will require more standard chemotherapy regimens
Clinical Consequences
  • Like all acute leukemias the clinical consequences of ALL are largely the result of bone marrow infiltration, potentially leading to bone pain as well as a myelophthisic anemia with consequent pancytopenia. Infiltration of the spleen, liver, and lymph nodes can result in splenomegaly, hepatomegaly, and painless lymphadenopathy. In a minority of cases, seeding of the CNS can result in neurological impairments. A unique feature of AML, especially the M3 APL subtype, is its propensity to trigger DIC, caused by extrusion of the cell's highly thrombogenic cytoplasmic granules into the blood. In general AML follows an extremely rapid course and the prognosis is relatively poor even with chemotherapeutic treatment.