Y-Chromosome Genes Strongly Expressed in Acute Myeloid Leukaemia.

In hematopoietic stem cell transplantation (HSCT) the gender of the donors has a substantial impact on the relapse rate, graft-versus-host reaction and overall therapeutic outcome. In several studies including our own HLA-haploidentical setting female to male transplantation seemed to be superior to other gender combinations, suggesting the dominance of Y-encoded minor histocompatibility antigens for graft-versus-leukemia reactions. In order to explore the therapeutic possibilities we compared the Y-chromosomal gene expression between isolated AML blasts (FAB M4/M5) and isolated CD14⁺ cells from healthy male donors. RNA was isolated and subsequently analyzed by low density arrays (LDAs), a real time-PCR based method. This way we could identify four Y-encoded genes found to be strongly up-regulated in the AML samples. Bcorl2, a pseudogene; pcdh11y, known to be involved in acquisition of apoptotic resistance in prostate cancer; tgif2ly and vcy, both putative transcription factors. The genes were cloned in plasmids and transferred in 293 cells. The expression of these proteins was analyzed by western blot. Biostatistical soft ware was used to predict the proteasomal cleavage site and binding capacity to HLA-A 0201 of these peptides. Five peptides were found to bind strongly to HLA-A 0201; they are now studied for recognition by female T cells. In summary, the genes identified might be involved in the immune recognition of AML blasts and other tumor cells. These peptides may help to identify and select T memory cells specific for AML blasts.