ANÁLISIS DE LA EXPRESIÓN DE LOS ANTÍGENOS TESTICULARES DE CÁNCER EN LEUCEMIA MIELOIDE CRÓNICA

Abstract

Cancer-testis antigens (CTAs) are expressed in a variety of cancers, but not in normal adult tissues, except for germ cells of the testis, and hence appear to be ideal targets for immunotherapy. The objective was to study the role of cancer-testis antigens as targets for immunotherapy and the relationship between corresponding gene expression and biologic behavior of chronic myeloid leukemia (CML). We screened 8 hematologic cell lines (K562, HL-60, Molt-4, Reh, Jurkat, Raji, Ramos, U-937), bone marrow (BM) samples from 10 healthy donors, testicular tissue and 65 CML patients by transcriptase-polymerase chain reaction (RT-PCR) and western-blot for the expression of 8 CTAs (MAGE-A3, MAGE-A4, MAGE-B2 MAGE-C1, BAGE-1, GAGE-2, LAGE-1 and NY-ESO-1). In hematologic cell lines we detected the expression that were absent from normal BM, in K562 was detected all CTA, in HL-60 was detected MAGE-A3, MAGE-B2 and GAGE-2, in Reh MAGE-A3, in U-937 GAGE-2 the rest of cell lines expressed none CTA. The frequencies at which CTAs were found to be expressed in CML patients were MAGE-A3 32,3%, MAGE-B2 1,5%, MAGE-C1 3,0%, MAGE-A4 63,6%, BAGE-1 6,6%, GAGE-2 20,0%, LAGE-1 13,3% and NY-ESO-1 36,6%. In these samples, the expression of some genes correlated with several clinicopathαological parameters, leucocytes and platelets for MAGE-C1 p= 0.014, p=0,002 respectively, sex for MAGE-A3 p=0,018 and finally platelets for LAGE-1 p= 0,001. There was no relationship between CTAs expression and prognosis. The MAGE-A3 protein was detected in some positive samples of mRNA. In addition, we examinated some CML samples treated with 10 conventional chemotherapeutics (Hydrea and INF-α) and 13 Tirosine cinase inhibitors (Imatinib, Nilotinib and Dasatinib). There was an increased expression of MAGE-A3 in both tirosine cinase inhibitors (69,2%) and conventional treatments (50,0%), MAGE.A4 53,8% and 20,0%, NY-ESO-1 0% and 20,0%. These genes serve as targets for antigen-specific immunotherapy in CML. CTAs antigens-specific immunotherapy might represent a promising approach for the eradication of residual therapy-resistant leukemic cells due to its frequent expression and stability under imatinib treatment.