Simultaneous expression of different immunogenic antigens in acute myeloidleukemia

Objective. Identification of immunogenic leukemia-associated antigens as ta rget structures is mandatory for specific immunotherapy of leukemia. Here, we define acute myeloid leukemia (AML) antigens eliciting a humoral immune response in the autologous host. Materials and Methods. We applied the method of serologic screening of cDNA expression libraries with autologous serum (SEREX). To date, this techniqu e has been used to characterize antigen structures in solid tumors. The mRN A expression pattern of these newly in AML isolated antigens and previously described leukemia antigens (PRAME, MACE-1, and Wt-1) was evaluated by rev erse transcriptase polymerase chain reaction. For Wt-1, Western blotting al so was performed. Results. Screening of a cDNA expression library prepared from a patient wit h AML FAB M2 using autologous and allogeneic sera, followed by sequencing o f positive clones, yielded three autoantigens (Prp1p/Zer1p, L19H1, and one without homology to previously described genes) and two antigens reactive w ith allogeneic sera (MAZ, PINCH). FRAME mRNA was expressed in 47% of 34 AML patients, but not in 13 CD34(+) cell samples or in peripheral blood mononu clear cells of 13 healthy volunteers. mRNA expression of MAZ was detected i n 44% of AML patients, but only in 8% of healthy donors. Humoral responses to MAZ were detected in 35%. More than 80% of the screened AML patients sho wed simultaneous expression of two or more of these antigens. Conclusions. Differential expression in AML patients vs healthy volunteers suggests that the immunogenic antigens FRAME and MAZ are potential candidat es for immunotherapy in AML. (C) 2000 International Society for Experimenta l Hematology. Published by Elsevier Science Inc.