Characterization of Bone Marrow Mast Cells in RUNX1-RUNX1T1 Acute Myeloid Leukemia
Sheeja T Pullarkat, Vinod A Pullarkat, Anand Lagoo, Wengang Chen, Victoria Bedell, Russell Brynes, Steven Yea, Qin Huang, Young Kim. UCLA, David Geffen School of Medicine, Los Angeles, CA; USC -Keck School of Medicine, Los Angeles, CA; Duke University Medical Center, Durham, NC; City of Hope National Medical Center, Duarte, CA
Background: Mast cells are commonly seen in the bone marrow of patients with RUNX1-RUNX1T1 AML. The purpose of this study was to characterize the immuophenotypic and molecular characteristics of these mast cells in order to better elucidate their role in leukemogenesis.
Design: 39 cases of RUNX1-RUNX1T1 AML' were evaluated. Mast cells were identified by IHC for tryptase. KIT mutation analysis was performed on genomic DNA extracted from bone marrow using PCR and direct sequencing of exons 8 and 17. Targeted-FISH was performed on mast cells using probes for RUNX1-RUNX1T1.
Results: Of the 39 cases, 28 cases showed <5 % mast cells, six showed 5-10%, two showed 11-20%, and one showed 25% mast cells. In 27 cases where KIT mutation analyses could be performed, four cases were positive for exon 17 mutation, and one was positive for exon 8 mutation and the remaining were wild type. In all of these KIT mutation positive cases, the number of mast cells ranged from 1-5% as measured by tryptase staining. In 5 cases where targeted-FISH analysis was performed, t(8;21) translocation was detected in mast cells in all 5 cases.
Conclusions: Our results show that tryptase staining is required to accurately quantitate bone marrow mast cells in RUNX1-RUNX1T1 AML. Nineteen percent (5/27) of RUNX1-RUNX1T1 AML were positive for KIT mutations at exons 8 or 17. However there was no association between KIT mutations and the number of mast cells in the bone marrow. Therefore mast cell hyperplasia cannot be used as a surrogate marker for KIT mutations in RUNX1-RUNX1T1 AML. Target-FISH analysis showed RUNX1-RUNX1T1 translocation on both myeloblasts and mast cells in 5/5 cases examined. However these mast cell infiltrates were normal on morphology and immunophenotype and did not fulfill the criteria for systemic mastocytosis. Additional studies are required to correlate the degree of bone marrow mast cell infiltration in RUNX1-RUNX1T1 AML with prognosis and clinical outcome.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 209, Tuesday Morning