Abstract 2682: New diagnostic and therapeutic target KU-MEL9 for chronic myeloid leukemia (CML)

Abstract

Overall survival of patients with chronic myeloid leukemia (CML) has dramatically changed over past ten years by the introduction of targeted therapy with tyrosine kinase inhibitors (TKIs). However, it has been reported that more than half of patients eventually relapse after the cessation of TKIs, suggesting that CML cells including leukemic stem cell (LSC) cannot be completely eradicated by TKIs. To this end, the identification of targets expressed in LSC is crucial for developing highly effective therapies for CML. In this study, we evaluated the gene expression of cancer testis antigen KU-MEL9, which was found in melanoma research, in a variety of human cell lines. This gene was highly expressed in several cell lines of hematological malignancies including CML and multiple myeloma (MM). We then investigated the gene expression of KU-MEL9 in bone marrow samples from 20 CML patients by standard RT-PCR method. Gene expression of KU-MEL9 were found in 17 patients (85%), and correlated with the expression of BCR-ABL fusion gene in most of the cases. On the other hand, 6 samples from normal donors didn't express this gene. In 2 CML patients who achieved a molecular remission with imatinib, the expression of KU-MEL9 gene was still observed, although BCR-ABL gene was not detected. It suggested that KU-MEL9 was expressed in residual CML cells including LSC and could be a more sensitive biomarker for CML patients. We also examined the possibility of KU-MEL9 being as a target of cytotoxic T cells (CTL) for immunotherapy to eradicate remaining LSCs after TKI treatment. Although this study had limited number of patient sample, KU-MEL9 may be a useful target for diagnosis and treatment for CML patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2682. doi:1538-7445.AM2012-2682