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Blood, 15 December 2006, Vol. 108, No. 13, pp. 4109-4117.
Prepublished online as a Blood First Edition Paper on August 24, 2006; DOI 10.1182/blood-2006-01-023127.
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IMMUNOBIOLOGY
Expression of tumor-associated antigens in acute myeloid leukemia: implications for specific immunotherapeutic approaches
Jochen Greiner,
Michael Schmitt,
Li Li,
Krzysztof Giannopoulos,
Katrin Bosch,
Anita Schmitt,
Konstanze Dohner,
Richard F. Schlenk,
Jonathan R. Pollack,
Hartmut Dohner, and
Lars Bullinger
From the Department of Internal Medicine III and the Department of Otorhinolaryngology Department, University of Ulm, Germany; and the Department of Pathology, Stanford University, Stanford, CA.
The expression of tumor-associated antigens (TAAs) might play a critical role in the control of minimal residual disease (MRD) in acute myeloid leukemia (AML), and therefore might be associated with clinical outcome in AML. In a DNA microarray analysis of 116 AML samples, we found a significant correlation between high mRNA levels of G250/CA9 and longer overall survival (P = .022), a similar trend with high mRNA levels of PRAME (P = .103), and a hint for RHAMM/HMMR. In contrast, for other TAAs like WT1, TERT, PRTN3, BCL2, and LAMR1, we found no correlation with clinical outcome. High expression of at least 1 of the 3 TAAs, RHAMM/HMMR, PRAME, or G250/CA9, provided the strongest favorable prognostic effect (P = .005). Specific T-cell responses were detected in 8 (47%) of 17 patients with AML in complete remission for RHAMM/HMMR-R3 peptide, in 7 (70%) of 10 for PRAME-P3 peptide, and in 6 (60%) of 10 for newly characterized G250/CA9-G2 peptide, a significant increased immune response compared with patients with AML patients who had refractory disease (P < .001). Furthermore, we could demonstrate specific lysis of T2 cells presenting these epitope peptides. In conclusion, expression of the TAAs RHAMM/HMMR, PRAME, and G250/CA9 can induce strong antileukemic immune responses, possibly enabling MRD control. Thus, these TAAs represent interesting targets for polyvalent immunotherapeutic approaches in AML.
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