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首页> 外文期刊>Clinical nutrition >Response to the letter to the editor 'the use of oral nutritional supplements in patients with head and neck cancer receiving (chemo)radiotherapy'.
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Response to the letter to the editor 'the use of oral nutritional supplements in patients with head and neck cancer receiving (chemo)radiotherapy'.

机译：致编辑的信“在接受（化学）放疗的头颈癌患者中使用口服营养补充剂”。

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Despite advances in allogeneic stem cell transplantation, BCR-ABL-positive acute lymphoblastic leukaemia (ALL) remains a high-risk disease, necessitating the development of novel treatment strategies. As the known oncomir, miR-17~92, is regulated by BCR-ABL fusion in chronic myeloid leukaemia, we investigated its role in BCR-ABL translocated ALL. miR-17~92-encoded miRNAs were significantly less abundant in BCR-ABL-positive as compared to -negative ALL-cells and overexpression of miR-17~19b triggered apoptosis in a BCR-ABL-dependent manner. Stable isotope labelling of amino acids in culture (SILAC) followed by liquid chromatography and mass spectroscopy (LC-MS) identified several apoptosis-related proteins including Bcl2 as potential targets of miR-17~19b. We validated Bcl2 as a direct target of this miRNA cluster in mice and humans, and, similar to miR-17~19b overexpression, Bcl2-specific RNAi strongly induced apoptosis in BCR-ABL-positive cells. Furthermore, BCR-ABL-positive human ALL cell lines were more sensitive to pharmacological BCL2 inhibition than negative ones. Finally, in a xenograft model using patient-derived leukaemic blasts, real-time, in vivo imaging confirmed pharmacological inhibition of BCL2 as a new therapeutic strategy in BCR-ABL-positive ALL. These data demonstrate the role of miR-17~92 in regulation of apoptosis, and identify BCL2 as a therapeutic target of particular relevance in BCR-ABL-positive ALL.
机译：尽管同种异体干细胞移植取得了进展，但BCR-ABL阳性的急性淋巴细胞白血病（ALL）仍然是高危疾病，需要开发新的治疗策略。由于已知的癌基因miR-17〜92在慢性粒细胞白血病中受到BCR-ABL融合的调控，因此我们研究了其在BCR-ABL易位ALL中的作用。与阴性的ALL细胞相比，miR-17〜92编码的miRNA在BCR-ABL阳性中的丰度明显降低，miR-17〜19b的过表达以BCR-ABL依赖性的方式触发了细胞凋亡。稳定的培养物中氨基酸同​​位素标记（SILAC），然后进行液相色谱和质谱（LC-MS），鉴定了几种凋亡相关蛋白，包括Bcl2作为miR-17〜19b的潜在靶标。我们验证了Bcl2作为小鼠和人类中该miRNA簇的直接靶标，并且类似于miR-17〜19b的过表达，Bcl2特异性RNAi强烈诱导BCR-ABL阳性细胞凋亡。此外，BCR-ABL阳性的人ALL细胞系对药理性BCL2抑制作用比阴性细胞更敏感。最后，在使用患者来源的白血病母细胞的异种移植模型中，实时体内成像证实BCL2的药理抑制是BCR-ABL阳性ALL的新治疗策略。这些数据证明了miR-17〜92在调节细胞凋亡中的作用，并鉴定出BCL2是与BCR-ABL阳性ALL特别相关的治疗靶标。

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