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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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Submitted January 19, 2006
Accepted July 25, 2006

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

Department of Internal Medicine III, University of Ulm, Germany
ENT Department, University of Ulm, Germany
Department of Pathology, Stanford University, California, USA

* Corresponding author; email: jochen.greiner{at}uniklinik-ulm.de.

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=0.022), a similar trend with high mRNA levels of PRAME (P=0.103), 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 one of the three TAAs, RHAMM/HMMR, PRAME or G250/CA9, provided the strongest favorable prognostic effect (P=0.005). Specific T-cell responses were detected in 8/17 (47%) AML patients in complete remission for RHAMM/HMMR-R3-derived, in 7/10 (70%) for PRAME-P3-derived, and in 6/10 (60%) for newly characterized G250/CA9-G2-derived peptides, a significant increased immune response compared to AML patients with refractory disease (P<0.001). 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 anti-leukemic immune responses, possibly enabling MRD control. Thus, these TAAs represent interesting targets for polyvalent immunotherapeutic approaches in AML.


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