INTERFERON ALPHA-INDUCED BIOLOGICAL RESPONSES IN CML

根据申请者的摘要改编的描述)：本提案基于 在染色体重排或其他突变破坏后的前提 其调控，EVI1在CML细胞中异常表达并协同作用 与bcr/abl预先存在的癌基因一起提供高度增殖和 侵袭性白血病克隆对控制细胞的细胞因子不起作用 生长或分化。通过使用分子和生物的组合 并通过比较EVI1和MDS1/EVI1的效果，建议 确定EVI1靶向的基因及其抑制机制 干扰素α诱导的反应。最后，申请者将开始一项未来的 慢性粒细胞白血病患者EVI1表达的研究证实 干扰素α治疗耐药患者的预后标志物。有能力 确定对IFNAlpha治疗无效的CML患者将是一个非常重要的问题 有价值的临床工具，可能会影响他们的治疗和整体 生死存亡。

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.