Kimura Hiroyuki, Onozawa Masahiro, Yoshida Shota, Miyashita Naoki, Yokoyama Shota, Matsukawa Toshihiro, Hirabayashi Shinsuke, Goto Hideki, Endo Tomoyuki, Oguri Satoshi, Fujisawa Shinichi, Mori Akio, Kondo Takeshi, Hidaka Daisuke, Okada Kohei, Ota Shuichi, Kakinoki Yasutaka, Tsutsumi Yutaka, Yamamoto Satoshi, Miyagishima Takuto, Hashiguchi Junichi, Nagashima Takahiro, Ibata Makoto, Wakasa Kentaro, Haseyama Yoshihito, Fujimoto Katsuya, Ishihara Toshimichi, Sakai Hajime, Teshima Takanori
Department of Hematology, Hokkaido University Faculty of Medicine, Graduate School of Medicine, Kita 15, Nishi 7, Kita-Ku, Sapporo, 0608638, Japan.
Department of Pediatrics, Hokkaido University Hospital, Sapporo, Japan.
Ann Hematol. 2023 Nov;102(11):3103-3113. doi: 10.1007/s00277-023-05405-0. Epub 2023 Aug 19.
IKZF1 deletion is a recurrent genomic alteration in B-cell acute lymphoblastic leukemia (B-ALL) and is divided into dominant-negative (DN) and loss of function (LOF) deletions. The prognostic impact of each deletion has not been fully elucidated. We retrospectively analyzed 117 patients with adult B-ALL including 60 patients with BCR::ABL1-positive B-ALL and 57 patients with BCR::ABL1-negative B-ALL by the fluorescence in situ hybridization (FISH) method for IKZF1 deletion and multiplex PCR for the 4 most common IKZF1 deletions (∆4-7, ∆2-7, ∆2-8, and ∆4-8). Samples, in which IKZF1 deletion was detected by FISH but a specific type of deletion was not identified by the PCR, were categorized as "other." Patients were classified into a DN group that had at least 1 allele of ∆4-7 (n = 23), LOF and other group (n = 40), and wildtype group (n = 54). DN type IKZF1 deletions were found in 33.3% of BCR::ABL1-positive cases and 5.2% of BCR::ABL1-negative cases. LOF and other type IKZF1 deletions were found in 43.4% of BCR::ABL1-positive cases and 24.6% of BCR::ABL1-negative cases. Patients with the DN group showed significantly higher overall survival (OS) than that of the LOF and other and WT groups (P = 0.011). Multivariate analysis including age, WBC counts, complex karyotype, and DN type IKZF1 deletion showed that the DN type of IKZF1 deletion (HR = 0.22, P = 0.013) had a positive impact and age ≥ 65 (HR = 1.92, P = 0.029) had a negative impact on OS. The prognostic impact of IKZF1 deletion depends on the type of deletion and DN type of IKZF1 deletion showed better prognosis in adult B-ALL patients.Clinical trial registration This study was part of a prospective observational study (Hokkaido Leukemia Net, UMIN000048611). It was conducted in compliance with ethical principles based on the Helsinki Declaration and was approved by the institutional review board of Hokkaido University Hospital (#015-0344).
IKZF1缺失是B细胞急性淋巴细胞白血病（B-ALL）中一种常见的基因组改变，分为显性负性（DN）缺失和功能丧失（LOF）缺失。每种缺失对预后的影响尚未完全阐明。我们采用荧光原位杂交（FISH）法检测IKZF1缺失，并对4种最常见的IKZF1缺失（∆4-7、∆2-7、∆2-8和∆4-8）进行多重PCR，对117例成人B-ALL患者进行回顾性分析，其中包括60例BCR::ABL1阳性B-ALL患者和57例BCR::ABL1阴性B-ALL患者。通过FISH检测到IKZF1缺失但PCR未鉴定出特定缺失类型的样本归类为“其他”。患者分为DN组（至少有1个∆4-7等位基因，n = 23）、LOF和其他组（n = 40）以及野生型组（n = 54）。在33.3%的BCR::ABL1阳性病例和5.2%的BCR::ABL1阴性病例中发现了DN型IKZF1缺失。在43.4%的BCR::ABL1阳性病例和24.6% 的BCR::ABL1阴性病例中发现了LOF和其他型IKZF1缺失。DN组患者的总生存期（OS）显著高于LOF和其他组以及WT组（P = 0.011）。包括年龄、白细胞计数、复杂核型和DN型IKZF1缺失在内的多变量分析显示，DN型IKZF1缺失（HR = 0.22，P = 0.013）对OS有积极影响，而年龄≥65岁（HR = 1.92，P = 0.029）对OS有负面影响。IKZF1缺失对预后的影响取决于缺失类型，DN型IKZF1缺失在成人B-ALL患者中显示出更好的预后。临床试验注册 本研究是一项前瞻性观察性研究（北海道白血病网络，UMIN000048611）的一部分。该研究按照基于《赫尔辛基宣言》的伦理原则进行，并获得了北海道大学医院机构审查委员会的批准（#015-0344）。
