Blood:PIM抑制或可改善IL7反应性CD127+ T-ALL和T-LBL患者化疗预后

2020-02-16 QQY MedSci原创

T细胞急性淋巴细胞白血病和淋巴瘤(T-ALL/T-LBL)是侵袭性的血液恶性肿瘤,目前采用高剂量化疗治疗。近年来,针对T-ALL/T-LBL患者的新型低毒性治疗策略的研究主要集中在肿瘤细胞的细胞内在特性的识别上。但非细胞自主激活的特定致癌途径也可能提供治疗靶点,可以在治疗水平上进行研究。在本研究中,Smedt等人发现内源性IL7可以增加CD127+ T-ALL/T-LBL中致癌激酶PIM1的表达,

T细胞急性淋巴细胞白血病淋巴瘤(T-ALL/T-LBL)是侵袭性的血液恶性肿瘤,目前采用高剂量化疗治疗。近年来,针对T-ALL/T-LBL患者的新型低毒性治疗策略的研究主要集中在肿瘤细胞的细胞内在特性的识别上。但非细胞自主激活的特定致癌途径也可能提供治疗靶点,可以在治疗水平上进行研究。

在本研究中,Smedt等人发现内源性IL7可以增加CD127+ T-ALL/T-LBL中致癌激酶PIM1的表达,从而使这些肿瘤细胞对体内PIM抑制敏感。通过不同的CD127+ T-ALL/T-LBL异种移植模型,研究人员还发现,短期化疗后体内残留的肿瘤细胞与未处理的肿瘤细胞相比,PIM1表达一致上调。

值得注意的是,这种效果短暂,因为在废除初始化疗后,在复发的疾病中没有观察到PIM1水平升高。此外,研究人员发现这种现象,至少部分,是由糖皮质激素在T-ALL/T-LBL PDX细胞中引起IL7RA转录上调的能力介导的,最终通过内源性IL7导致非细胞自主PIM1上调。

最后,研究人员在体内证明与化疗联合pan-PIM抑制剂科提高CD127+ T-ALL的PDX模型的白血病存活率。

总而言之,本研究揭示了IL7和糖皮质激素协同驱动PIM1异常激活,提示IL7反应性CD127+ T-ALL和T-LBL患者在诱导化疗期间可受益于PIM抑制。

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    2020-03-04 lqrandywkz
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    2020-02-18 膀胱癌
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    2020-02-18 紫砂壶