Kicinski Michal, Arfeuille Chloé, Grardel Nathalie, Bakkus Marleen, Caye-Eude Aurélie, Plat Geneviève, Ferster Alina, Uyttebroeck Anne, De Moerloose Barbara, Rohrlich Pierre, Suciu Stefan, Bertrand Yves, Cavé Hélène
EORTC Headquarters, Brussels, Belgium.
Département de Génétique, Hôpital Robert Debré, Assistance Publique des Hôpitaux de Paris (AP-HP), Paris, France.
Pediatr Blood Cancer. 2023 Jun;70(6):e30313. doi: 10.1002/pbc.30313. Epub 2023 Mar 27.
IKZF1 gene deletion is an indicator of poor prognosis in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The AEIOP/BFM group proposed that the prognostic strength of IKZF1 deletion could be remarkably improved by taking into account additional genetic deletions and reported that among patients with an IKZF1 deletion those with deletions in CDKN2A/2B, PAX5, or PAR1 in the absence of ERG deletion, grouped as IKZF1 , had the worst outcome.
Between 1998 and 2008, 1636 patients under 18 years of age with previously untreated BCP-ALL were registered in the EORTC 58951 trial. Those with multiplex ligation-dependent probe amplification data were included in this analysis. Unadjusted and adjusted Cox model was used to investigate the additional prognostic value of IKZF1 .
Among 1200 patients included in the analysis, 1039 (87%) had no IKZF1 deletion (IKZF1 ), 87 (7%) had an IKZF1 deletion but not IKZF1 (IKZF1 ) and 74 (6%) had IKZF1 . In the unadjusted analysis, both patients with IKZF1 (hazard ratio [HR] = 2.10, 95% confidence interval [CI]: 1.34-3.31) and IKZF1 (HR = 3.07, 95% CI: 2.01-4.67) had a shorter event-free survival compared with IKZF1 . However, although the IKZF1 status was associated with patients' characteristics indicating poor prognosis, the difference between IKZF1 and IKZF1 was not statistically significant (HR = 1.46, 95% CI: 0.83-2.57, p = .19). The results of the adjusted analysis were similar to the unadjusted analysis.
In patients with BCP-ALL from the EORTC 58951 trial, the improvement of the prognostic importance of IKZF1 by considering IKZF1 was not statistically significant.
IKZF1基因缺失是儿童B细胞前体急性淋巴细胞白血病（BCP-ALL）预后不良的一个指标。AEIOP/BFM研究组提出，通过考虑其他基因缺失情况，IKZF1缺失的预后强度可得到显著改善，并报告称，在IKZF1缺失的患者中，那些在无ERG缺失情况下伴有CDKN2A/2B、PAX5或PAR1缺失的患者（归类为IKZF1 ）预后最差。
1998年至2008年期间，1636例18岁以下初治BCP-ALL患者登记入EORTC 58951试验。本分析纳入了有多重连接依赖探针扩增数据的患者。采用未调整和调整后的Cox模型来研究IKZF1的额外预后价值。
在纳入分析的1200例患者中，1039例（87%）无IKZF1缺失（IKZF1 ），87例（7%）有IKZF1缺失但非IKZF1 （IKZF1 ），74例（6%）有IKZF1 。在未调整分析中，与IKZF1 患者相比，IKZF1 患者（风险比[HR]=2.10，95%置信区间[CI]：1.34 - 3.31）和IKZF1 患者（HR = 3.07，95% CI：2.01 - 4.67）的无事件生存期均较短。然而，尽管IKZF1状态与提示预后不良的患者特征相关，但IKZF1 和IKZF1 之间的差异无统计学意义（HR = 1.46，95% CI：0.83 - 2.57，p = 0.19）。调整分析结果与未调整分析相似。
在EORTC 58951试验的BCP-ALL患者中，通过考虑IKZF1 来提高IKZF1预后重要性的差异无统计学意义。
