针对慢性淋巴细胞白血病和急性髓系白血病的治疗，抗凋亡蛋白BCL-2的特异性抑制剂BH3模拟药物Venetoclax已经取得了临床成功。目前的关注已经转向与其相关的促生存BCL-2家族成员，假设针对这些蛋白质的新的BH3模拟药物可能会模拟Venetoclax的成功。针对促生存MCL-1或BCL-XL的BH3模拟剂已经进入临床试验，但管理靶点毒性具有挑战性。虽然越来越多的证据表明BFL-1/A1是血液恶性肿瘤中多种化疗药物和BH3模拟药物的耐药因子，但很少有研究探讨BCL-W在癌症发展、扩张和治疗反应中的作用。我们之前发现，在各种已建立的人类Burkitt淋巴瘤和弥漫性大B细胞淋巴瘤细胞系中，并不需要BCL-W来维持细胞的存活和生长。然而，对于BCL-W是否影响淋巴瘤的发展仍存在疑问。在这里，我们展示了BCL-W对MYC驱动的淋巴瘤发生并不是必需物，且在没有BCL-W的情况下形成的肿瘤对BCL-2家族成员表达没有补偿性改变，对BH3模拟药物的敏感性也没有改变。这些结果表明，BCL-W在MYC驱动的淋巴瘤的发展以及这些肿瘤对抗癌药物的反应中并不起主要作用。©2023.作者或许可方

The BH3-mimetic drug Venetoclax, a specific inhibitor of anti-apoptotic BCL-2, has had clinical success for the treatment of chronic lymphocytic leukaemia and acute myeloid leukaemia. Attention has now shifted towards related pro-survival BCL-2 family members, hypothesising that new BH3-mimetic drugs targeting these proteins may emulate the success of Venetoclax. BH3-mimetics targeting pro-survival MCL-1 or BCL-XL have entered clinical trials, but managing on-target toxicities is challenging. While increasing evidence suggests BFL-1/A1 is a resistance factor for diverse chemotherapeutic agents and BH3-mimetic drugs in haematological malignancies, few studies have explored the role of BCL-W in the development, expansion, and therapeutic responses of cancer. Previously, we found that BCL-W was not required for the ongoing survival and growth of various established human Burkitt lymphoma and diffuse large B cell lymphoma cell lines. However, questions remained about whether BCL-W impacts lymphoma development. Here, we show that BCL-W appears dispensable for MYC-driven lymphomagenesis, and such tumours arising in the absence of BCL-W show no compensatory changes to BCL-2 family member expression, nor altered sensitivity to BH3-mimetic drugs. These results demonstrate that BCL-W does not play a major role in the development of MYC-driven lymphoma or the responses of these tumours to anti-cancer agents.© 2023. The Author(s).