Department of Human Genetics, Hannover Medical School, Hannover, Germany.
Department of Pediatrics, University Hospital Schleswig-Holstein, Kiel, Germany.
Genes Chromosomes Cancer. 2020 Nov;59(11):667-671. doi: 10.1002/gcc.22882. Epub 2020 Jul 7.
PAX5 is a member of the paired box (PAX) family of transcription factors involved in B-cell development. PAX5 has recently been described as a distinct genetic B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) subtype with a favorable prognosis in adults. In contrast, an unfavorable outcome has been observed in children. Our aim was to determine the frequency of PAX5 in childhood BCP-ALL treated according to the Associazione Italiana Ematologia ed Oncologia Pediatrica-Berlin-Frankfurt-Muenster (AIEOP-BFM) ALL 2000 protocol and to evaluate its clinical significance within this study cohort. The analyses included 1237 patients with ALL treated in the AIEOP-BFM ALL 2000 trial with complete information for copy number variations (CNVs) of IKZF1, PAX5, ETV6, RB1, BTG1, EBF1, CDKN2A, CDKN2B, and ERG. A customized TaqMan genotyping assay was used to screen for PAX5 . Sanger sequencing was used to confirm PAX5 -positive results as well as to screen for second variants in PAX5. Agilent CGH + SNP arrays (e-Array design 85 320; Agilent Technologies) were performed in PAX5 -positive patients to verify additional CNVs. Almost 2% (20/1028) of our BCP-ALL cohort were PAX5 -positive. White blood cell counts higher than 50 000/μl as well as male sex were significantly (P < .05) associated with PAX5 . Most of the PAX5 -positive cases were 10 years of age or older. PAX5 -positive samples were enriched for deletions affecting PAX5, IKZF1, CDKN2A, and CDKN2B. Compared to PAX5 -wildtype BCP-ALL, PAX5 -positive patients showed a significantly reduced 5-year overall survival (P = .042). Further studies should evaluate the interaction of PAX5 with other genetic aberrations to further stratify intermediate risk pediatric BCP-ALL.
PAX5 是参与 B 细胞发育的配对盒（PAX）家族转录因子的成员。PAX5 最近被描述为一种独特的遗传 B 细胞前体（BCP）急性淋巴细胞白血病（ALL）亚型，在成人中预后良好。相比之下，在儿童中观察到不良结局。我们的目的是确定根据意大利血液学和肿瘤学会儿科分会-柏林-法兰克福-慕尼黑（AIEOP-BFM）ALL 2000 方案治疗的儿童 BCP-ALL 中 PAX5 的频率，并在该研究队列中评估其临床意义。该分析包括 1237 名接受 AIEOP-BFM ALL 2000 试验治疗的 ALL 患者，这些患者具有 IKZF1、PAX5、ETV6、RB1、BTG1、EBF1、CDKN2A、CDKN2B 和 ERG 拷贝数变异（CNVs）的完整信息。使用定制的 TaqMan 基因分型测定法筛查 PAX5。桑格测序用于确认 PAX5 阳性结果以及筛查 PAX5 中的第二个变体。在 PAX5 阳性患者中进行安捷伦 CGH+SNP 阵列（e-Array 设计 85320；安捷伦科技公司）以验证其他 CNVs。我们的 BCP-ALL 队列中几乎有 2%（20/1028）为 PAX5 阳性。白细胞计数高于 50000/μl 以及男性与 PAX5 显著相关（P <.05）。大多数 PAX5 阳性病例为 10 岁或以上。PAX5 阳性样本富集了影响 PAX5、IKZF1、CDKN2A 和 CDKN2B 的缺失。与 PAX5 野生型 BCP-ALL 相比，PAX5 阳性患者的 5 年总生存率显著降低（P =.042）。进一步的研究应评估 PAX5 与其他遗传异常的相互作用，以进一步分层儿童 BCP-ALL 的中间风险。
