上海交通大学医学院细胞分化和凋亡教育部重点实验室的研究人员发现,急性淋巴细胞白血病干细胞通过建造新的骨髓微环境逃避化疗。相关研究成果近日发表在《癌细胞》上。
据介绍,白血病的治疗主要依靠化疗,但化疗难以清除骨髓中的白血病干细胞,导致白血病容易复发。因此,回答化疗开始后骨髓中到底发生了什么?白血病干细胞如何逃避化疗等科学问题对研究治疗策略非常重要。
研究人员先将人急性淋巴细胞白血病细胞注入小鼠体内,建立白血病小鼠模型,之后给予化疗,用先进的成像技术等进行观察和研究。发现白血病细胞在骨髓中浸润性生长,在实质性破坏正常骨髓微环境后,给予化疗,白血病干细胞会分泌一些细胞因子,招募和改造骨髓间充质干细胞,建立一个临时的“庇护所”,逃避化疗杀伤。正如地震摧毁了房屋,幸存者搭建一个临时帐篷,度过灾难期。
研究者在骨髓里发现并鉴定了这个“临时帐篷”,并将这个新建的“庇护所”称为NSM 微环境。研究者发现,干扰NSM 微环境的形成或保护功能,可以明显提高化疗效果,清除骨髓中残留的白血病干细胞。同时,通过化疗不能缓解或部分缓解的白血病病人样本中,检测到这种微环境的标志物,在完全缓解的白血病人样本中却检测不到。
专家认为,该研究的意义在于:可以通过检测一种标志物来判断病人预后,并靶向干扰其形成或功能,从而提高化疗效果,甚至治愈白血病。同时,该研究也可能应用在其他肿瘤治疗中。
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