Department of Paediatrics, VIVA-NUS Centre for Translational Research in Acute Leukaemia , Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Viva-University Children's Cancer Centre, Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore.
Blood Adv. 2021 Dec 14;5(23):5226-5238. doi: 10.1182/bloodadvances.2021004895.
Among the recently described subtypes in childhood B-lymphoblastic leukemia (B-ALL) were DUX4- and PAX5-altered (PAX5alt). By using whole transcriptome RNA sequencing in 377 children with B-ALL from the Malaysia-Singapore ALL 2003 (MS2003) and Malaysia-Singapore ALL 2010 (MS2010) studies, we found that, after hyperdiploid and ETV6-RUNX1, the third and fourth most common subtypes were DUX4 (n = 51; 14%) and PAX5alt (n = 36; 10%). DUX4 also formed the largest genetic subtype among patients with poor day-33 minimal residual disease (MRD; n = 12 of 44). But despite the poor MRD, outcome of DUX4 B-ALL was excellent (5-year cumulative risk of relapse [CIR], 8.9%; 95% confidence interval [CI], 2.8%-19.5% and 5-year overall survival, 97.8%; 95% CI, 85.3%-99.7%). In MS2003, 21% of patients with DUX4 B-ALL had poor peripheral blood response to prednisolone at day 8, higher than other subtypes (8%; P = .03). In MS2010, with vincristine at day 1, no day-8 poor peripheral blood response was observed in the DUX4 subtype (P = .03). The PAX5alt group had an intermediate risk of relapse (5-year CIR, 18.1%) but when IKZF1 was not deleted, outcome was excellent with no relapse among 23 patients. Compared with MS2003, outcome of PAX5alt B-ALL with IKZF1 codeletion was improved by treatment intensification in MS2010 (5-year CIR, 80.0% vs 0%; P = .05). In conclusion, despite its poor initial response, DUX4 B-ALL had a favorable overall outcome, and the prognosis of PAX5alt was strongly dependent on IKZF1 codeletion.
在最近描述的儿童 B 淋巴细胞白血病（B-ALL）亚型中，包括 DUX4 和 PAX5 改变（PAX5alt）。通过对来自马来西亚-新加坡 ALL 2003（MS2003）和马来西亚-新加坡 ALL 2010（MS2010）研究的 377 名 B-ALL 患儿进行全转录组 RNA 测序，我们发现，在超二倍体和 ETV6-RUNX1 之后，第三和第四常见的亚型是 DUX4（n = 51；14%）和 PAX5alt（n = 36；10%）。在 44 例残留疾病不良的第 33 天（MRD）患者中，DUX4 也形成了最大的遗传亚型。但尽管 MRD 不良，DUX4 B-ALL 的预后仍极好（5 年累积复发风险[CIR]为 8.9%；95%置信区间[CI]为 2.8%-19.5%，5 年总生存率为 97.8%；95%CI 为 85.3%-99.7%）。在 MS2003 中，21%的 DUX4 B-ALL 患者在第 8 天泼尼松龙外周血反应不佳，高于其他亚型（8%；P =.03）。在 MS2010 中，第 1 天用长春新碱，在 DUX4 亚型中未观察到第 8 天外周血反应不良（P =.03）。PAX5alt 组复发风险中等（5 年 CIR 为 18.1%），但当 IKZF1 未缺失时，23 例患者中无一例复发，预后极好。与 MS2003 相比，在 MS2010 中强化治疗改善了 IKZF1 缺失的 PAX5alt B-ALL 的预后（5 年 CIR 为 80.0% vs 0%；P =.05）。总之，尽管 DUX4 B-ALL 初始反应不佳，但总体预后良好，而 PAX5alt 的预后强烈依赖于 IKZF1 缺失。
