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Systematic analysis of potential targets for immunotherapy in acute myeloid leukemia

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)

NHLBI

CANCER-4

Authors

  • M. Goswami
  • M. Bhagwat
  • L. Young
  • H.M. Sardon
  • A.L. Williams
  • J.P. McCoy
  • S. Ito
  • S.A. Strickland
  • B.N. Savani
  • J.W. Fraser
  • H. Sadrzadeh
  • A.T. Fathi
  • L. Qin
  • A. Hess
  • B.D. Smith
  • J.E. Karp
  • A.J. Barrett
  • C.S. Hourigan

Abstract

Treatment in the non-transplant setting for adults with acute myeloid leukemia (AML) depends on the ability to target leukemic clones while sparing normal tissues. Many leukemia-associated antigens (LAA) have been identified, but an evidence-based list of targets in AML has not been established. Thus, we profiled the expression of 75 LAAs from 48 de-identified, clinically annotated primary AML patients. Gene expression was assayed using RQ-PCR on custom-designed arrays. 8 blood samples were further characterized by flow sorting into bulk leukemia and enriched stem cell populations. 51 genes were over-expressed by at least 5-fold in at least one patient, and several distinct patterns of over-expression were observed in AML patients compared to healthy donors. The presence of the FLT3-ITD mutation was strongly statistically associated with high WT1 levels, and WT1-negative samples expressed significantly lower levels of ERG, BAALC, and KIT – all factors associated with poor prognosis in AML. The heterogeneity and patterns of over-expression observed suggest that targeting a single antigen is ineffective because of the vast diversity of disease, but based on our data, it may be possible to create a panel of multiple targets with coverage of all AMLs, eliminating the need for costly individualized personalization of therapy.

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