Are we ABL to do better for children with BCR-ABL1-like acute lymphocytic leukaemia?
Are we ABL to do better for children with BCR-ABL1-like acute lymphocytic leukaemia?
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DOI：
10.1016/s2352-3026(20)30362-8
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发表时间：
2021-01
期刊：
影响因子：
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通讯作者：
Tasian SK
中科院分区：
文献类型：
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作者：
Tasian SK
就在十年前，两个以儿科白血病为重点的研究小组独立地在高危、细胞遗传学正常的b细胞急性淋巴细胞白血病患儿中发现了现在称为bcr - abl1样（也称为费城染色体样）的急性淋巴细胞白血病，这些患儿在常规化疗下复发的风险非常高。1,2发现这些患者的白血病细胞具有激酶激活的基因表达谱，与BCR-ABL1融合阳性的急性淋巴细胞白血病相似，但前哨BCR-ABL1重排呈阴性。在过去的10年里，通过国家和国际合作的努力，bcr - abl1样急性淋巴细胞白血病的详细分子特征揭示了这种疾病3型的显著遗传异质性和特征组成激酶信号通路，并阐明了其在儿科到成人年龄段的发病率。大量临床前研究进一步表明，bcr - abl1样急性淋巴细胞白血病细胞在体外和体内对靶向酪氨酸激酶抑制剂表现出敏感性，这导致目前的早期临床试验评估酪氨酸激酶抑制剂在复发或新诊断的bcr - abl1样急性淋巴细胞白血病儿童和成人化疗之外的安全性和潜在疗效。4然而，回顾性鉴定的bcr - abl1样急性淋巴细胞白血病患儿的临床结果仍然不明确，这些患儿已经接受了最佳化疗方案的统一治疗。由于bcr - abl1样的相对罕见，目前的单实验治疗组临床试验设计需要进行潜在疗效评估，数据的缺乏给潜在疗效评估带来了明显的挑战
Just one decade ago, two paediatric leukaemia-focused research teams independently identified what is now known as BCR–ABL1-like (also known as Philadelphia chromosome-like) acute lymphocytic leukaemia among children with high-risk, cytogenetically normal B-cell acute lymphocytic leukaemia, who showed a very high risk of relapse with conventional chemotherapy. 1, 2 The leukaemic cells of these patients were found to harbour a kinase-activated gene expression profile similar to that of BCR–ABL1 fusion-positive acute lymphocytic leukaemia, yet they were negative for the sentinel BCR–ABL1 rearrangement. Over the past 10 years, detailed molecular characterisation of BCR–ABL1-like acute lymphocytic leukaemia via national and international collaborative efforts has revealed the remarkable genetic heterogeneity and characteristic constitutive kinase signalling pathways of this disease type3 and has elucidated its incidence across the paediatric-to-adult age spectrum. Numerous preclinical studies have further indicated that BCR–ABL1-like acute lymphocytic leukaemia cells show sensitivity to targeted tyrosine-kinase inhibitors in vitro and in vivo, which has led to current earlyphase clinical trials assessing the safety and potential efficacy of tyrosine-kinase inhibitors in addition to chemotherapy in children and adults with relapsed or newly-diagnosed BCR–ABL1-like acute lymphocytic leukaemia. 4 However, well defined clinical outcomes of retrospectively-identified children with BCR-ABL1-like acute lymphocytic leukaemia, who have been treated uniformly with the best available chemotherapy regimens, remain poorly defined. This absence of data has created appreciable challenges for potential efficacy assessment in current single experimental treatment group clinical trial designs, which have been required to date given the relative rarity of BCR–ABL1-like