INTERFERON ALPHA-INDUCED BIOLOGICAL RESPONSES IN CML

描述改编自申请人摘要）：本提案基于 前提是在染色体重排或其他突变破坏后， 其调节，EVI 1在CML细胞中不适当地表达，并协同 与BCR/ABL预先存在的癌基因结合， 侵袭性白血病克隆对细胞因子无反应 生长或分化。通过结合分子和生物学 测定，并通过比较EVI 1和MDS 1/EVI 1的作用，建议 确定EVI 1靶向的基因和EVI 1抑制的机制 IFN α诱导的反应。最后，申请人将开始一个前瞻性的 对CML患者的研究证实EVI 1的表达可用作 IFN α治疗耐药患者的预后标志物。的能力 识别对IFN α治疗无反应的CML患者将是一个非常重要的方法， 有价值的临床工具，可能会影响他们的治疗和他们的整体 生存

DESCRIPTION Adapted from the applicant's abstract): This proposal is based on the premise that after chromosomal rearrangements or other mutations disrupt its regulation, EVI1 is inappropriately expressed in CML cells and synergizes with the BCR/ABL pre-existing oncogene to give a highly proliferating and aggressive leukemic clone not responding to cytokines that control cellular growth or differentiation. By using a combination of molecular and biological assays, and by comparing the effects of EVI1 and MDS1/EVI1, it is proposed to identify the genes targeted by EVI1 and the mechanisms by which EVI1 inhibits IFNalpha-induced response. Finally, the applicant will begin a prospective study of CML patients to confirm that expression of EVI1 can be used as a prognostic marker for IFNalpha-therapy resistant patients. The ability to identify CML patients who will not respond to IFNalpha-therapy will be a very valuable clinical tool that could affect their treatment and their overall survival.