Hematopathology, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, California, USA.
Keck School of Medicine of University of Southern California, Los Angeles, California, USA.
Pediatr Blood Cancer. 2024 Jul;71(7):e30996. doi: 10.1002/pbc.30996. Epub 2024 Apr 18.
Compared to other ethnicities, Hispanics/Latinos (H/L) have a high incidence of acute lymphoblastic leukemia (ALL), enrichment of unfavorable ALL genetic subtypes, and worse outcomes, even after correcting for socioeconomic factors. We previously demonstrated increased incidence of the high-risk genetic drivers IKZF1 deletion and IGH::CRLF2 rearrangement in H/L compared to non-H/L children with B-ALL. Here in an expanded pediatric cohort, we sought to identify novel genetic drivers and secondary genetic alterations in B-ALL associated with H/L ethnicity.
Comprehensive clinicopathologic data from patients with B-ALL treated from 2016 to 2020 were analyzed. Subtype was determined from karyotype, fluorescence in situ hybridization (FISH), chromosome microarray (CMA), and our next-generation sequencing (NGS) panel (OncoKids). Non-driver genetic variants were also examined. p-Values less than .05 (Fisher's exact test) were considered significant.
Among patients with B-ALL at diagnosis (n = 273), H/L patients (189, 69.2%) were older (p = .018), more likely to present with CNS2 or CNS3 disease (p = .004), and NCI high-risk ALL (p = .014) compared to non-H/L patients. Higher incidence of IGH::CRLF2 rearrangement (B-ALL, BCR::ABL1-like, unfavorable; p = .016) and lower incidence of ETV6::RUNX1 rearrangement (favorable, p = .02) were also associated with H/L ethnicity. Among secondary (non-subtype-defining) genetic variants, B-ALL in H/L was associated with IKFZ1 deletion alone (p = .001) or with IGH::CRLF2 rearrangement (p = .003). The IKZF1 profile (IKZF1 deletion plus CDKN2A/2Bdel, PAX5del, or P2RY8::CRLF2 rearrangement without DUX4 rearrangement) was identified as a novel high-risk feature enriched in H/L patients (p = .001).
Our study shows enrichment of high-risk genetic variants in H/L B-ALL and raises consideration for novel therapeutic targets.
与其他族裔相比，西班牙裔/拉丁裔（H/L）的急性淋巴细胞白血病（ALL）发病率较高，ALL 遗传亚型丰富，预后较差，即使在纠正社会经济因素后也是如此。我们之前的研究表明，与非 H/L 儿童 B-ALL 相比，H/L 儿童中存在高风险遗传驱动因子 IKZF1 缺失和 IGH::CRLF2 重排的发生率增加。在此，我们在一个扩展的儿科队列中，试图确定与 H/L 族裔相关的 B-ALL 中新型遗传驱动因子和继发性遗传改变。
分析了 2016 年至 2020 年间接受治疗的 B-ALL 患者的综合临床病理数据。亚型由核型、荧光原位杂交（FISH）、染色体微阵列（CMA）和我们的下一代测序（NGS）面板（OncoKids）确定。还检查了非驱动基因变异。p 值小于 0.05（Fisher 确切检验）被认为具有统计学意义。
在诊断为 B-ALL 的患者中（n=273），H/L 患者（189 例，69.2%）年龄较大（p=0.018），更有可能出现 CNS2 或 CNS3 疾病（p=0.004），以及 NCI 高危 ALL（p=0.014）与非 H/L 患者相比。IGH::CRLF2 重排（B-ALL、BCR::ABL1 样、不良；p=0.016）发生率较高，而 ETV6::RUNX1 重排（有利，p=0.02）发生率较低也与 H/L 族裔有关。在次级（非亚型定义）遗传变异中，H/L 中的 B-ALL 与 IKZF1 缺失单独相关（p=0.001）或与 IGH::CRLF2 重排相关（p=0.003）。IKZF1 谱（IKZF1 缺失加 CDKN2A/2Bdel、PAX5del 或 P2RY8::CRLF2 重排无 DUX4 重排）被确定为 H/L 患者中丰富的新型高危特征（p=0.001）。
我们的研究表明 H/L B-ALL 中存在高风险遗传变异的富集，并提出了对新治疗靶点的考虑。
