acute monocytic leukemia

Acute monocytic leukemia is classified under the FAB system as AML-M5, further divided into M5a (poorly differentiated) and M5b (well-differentiated). It arises from malignant transformation of myeloid progenitor cells committed to the monocytic lineage, leading to accumulation of monoblasts and promonocytes in bone marrow and peripheral blood.

Pathophysiology: Leukemic monocytes/monoblasts infiltrate tissues due to their natural chemotactic and adhesive properties, leading to characteristic extramedullary manifestations including gingival hyperplasia/infiltration, skin (leukemia cutis), and CNS involvement. The disease is strongly associated with rearrangements of the MLL (KMT2A) gene at chromosome 11q23, which can occur de novo or secondary to prior chemotherapy with topoisomerase II inhibitors (e.g., etoposide), distinguishing it as a classic example of therapy-related AML.

Clinical features: Patients present with symptoms of bone marrow failure (anemia, thrombocytopenia, neutropenia) plus distinctive extramedullary findings: gum hypertrophy/bleeding, skin nodules, and higher incidence of DIC and CNS involvement compared to other AML subtypes. Monocytic markers include CD14, CD11b, CD11c, and nonspecific esterase (NSE) positivity on special stains, which helps distinguish it from other AML subtypes.

Lab findings: Elevated serum lysozyme (muramidase) is characteristic due to monocyte lineage. Peripheral smear shows monoblasts (large cells with folded/indented nuclei, abundant cytoplasm) and promonocytes.

Treatment: Standard AML induction chemotherapy (7+3 regimen: cytarabine + anthracycline), though monocytic subtypes may have variable prognosis depending on cytogenetics; MLL-rearranged cases often confer intermediate to poor prognosis.

Key associations for boards: MLL/KMT2A rearrangement (11q23), infant leukemias, secondary AML after epipodophyllotoxin (etoposide) therapy, gingival infiltration, NSE positivity, elevated lysozyme.