Abstract
3104 Background: The ability to target myeloid malignancies using immunotherapy, without allogeneic transplantation, depends on the capability to target leukemic clones while sparing normal tissues. A variety of putative leukemia associated antigens (LAA) have been identified but an evidence-based list of targets for acute myeloid leukemia (AML) has not yet been established. Methods: De-identified, clinically annotated, samples of peripheral blood and/or bone marrow aspirate from untreated AML patients were collected under IRB-approved protocols from three NCCN cancer centers. Samples were analyzed for commonly observed somatic mutations in ASXL1, DNMT3A, FLT3, IDH1/2, KIT, NPM1, NRAS, RUNX1, TET2, and WT1. Gene expression of 75 consensus LAAs were determined using a custom-designed RT-PCR array. 12 samples underwent extended LAA analysis by flow sorting into “bulk leukemia” and “stem cell enriched” populations. LAA expression was normalized using the geometric mean of three control genes. Results: Samples from 48 AML patients (30 blood, 22 marrow) were suitable for analysis. Average age of patients was 53 (24-86), 50% were female. Cytogenetics were favorable (17%), intermediate (65%) or adverse (19%); 29% presented with a white blood cell count >50,000. Over 10,000 individual data-points were collected. Five distinct patterns of LAA expression were observed in blood from AML patients compared to healthy donors. Conclusions: Understanding the heterogeneity and patterns of AML LAA expression between individuals allows the rational prioritization of potential targets for immunotherapy. Based on our data we predict that targeting any single LAA will likely often be ineffective but that it may be possible to create an inclusive panel of multiple targets with coverage of most AMLs, eliminating the need for individualized personalization of therapy. Such AML antigen signatures may also have utility for minimal residual disease monitoring. [Table: see text]
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