Occult Mastocytosis in AML with Inv(16) and Therapy-Related AML
Brock A Martin, Ryan C Johnson, Jason R Gotlib, Daniel A Arber, Tracy I George. Stanford University School of Medicine, Stanford, CA
Background: Our previous studies have demonstrated an increased incidence of occult mastocytosis in association with acute myeloid leukemia (AML) with t(8;21)(q22;q22). Furthermore, detection of KIT gene mutations in patients with core binding factor leukemias, AML with t(8;21)(q22;q22) and AML with inv(16)(p13q22), has been shown to impart a relatively unfavorable prognosis. We are currently conducting a retrospective analysis of a large series of patients with inv(16) AML, as well as patients with other poor prognosis leukemias, specifically therapy-related AML, looking for evidence of systemic mastocytosis not initially detected at diagnosis.
Design: Available diagnostic or relapsed bone marrow biopsy specimens were identified from 20 patients with inv(16) AML and 27 patients with therapy-related AML from our institutional database from 1988-2012. Diagnoses were confirmed based on morphology, flow cytometry, cytogenetic, and molecular studies. Mast cell morphology was evaluated by Wright-Giemsa stained aspirate smears. Immunohistochemical staining with an antibody to tryptase was performed on biopsies via an automated platform (Ventana Benchmark, Tucson, AZ). Additional immunohistochemical staining with antibodies to CD117 (c-kit) and CD25 was performed on biopsy samples which demonstrated increased mast cells by tryptase immunostaining.
Results: 3/20 patients with inv(16) AML and 2/27 patients with therapy-related AML showed an increase in mast cells on biopsy via tryptase staining. Of the inv(16) AML cases with increased mast cells, 1 of 3 patients met WHO criteria for indolent systemic mastocytosis. Upon further analysis, 2 cases of inv(16) AML and 2 cases of therapy-related AML showed mast cell hyperplasia with expression of CD117 and not CD25.
Conclusions: In comparison to AML with t(8;21), where we reported 4/41 (9.7%) of patients with occult systemic mastocytosis and 11/41 (26.8%) of patients with increased mast cells, we find an overall lower incidence of systemic mastocytosis (1/20; 5%) and increased mast cells (3/20; 15%) in patients with AML with inv(16), another core binding factor leukemia. In contrast, therapy-related AML does not have an increased incidence of systemic mastocytosis. Although preliminary, these findings argue that tryptase staining of specific types of AML (e.g. AML with t(8;21) and AML with inv(16)) may be more useful than in other acute leukemias, such as therapy-related AML. We are currently correlating results with KIT mutational analysis and clinical outcome.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 219, Wednesday Morning