RNA-seq from bone marrow samples of pediatric acute lymphoblastic leukemia patients at diagnosis. Integrative transcriptomic molecular characterization of pediatric acute lymphoblastic leukemia patients from a multicentric Argentinian study.

Pediatric acute lymphoblastic leukemia (ALL) is highly heterogeneous at the molecular level, with more than 20 molecular subtypes identified so far in B-ALL that are the basis for risk-adapted therapy and precision medicine. They are characterized by specific chromosomal rearrangements, gene expression profiles, aneuploidies and point mutations, and their identification relies on the technical availability in each center. In this context, increasing complexity of molecular classification implies technical, analytical and economic challenges that together limit their implementation, especially in low and middle income countries. In this work we applied transcriptome sequencing for molecular classification of B-ALL at diagnosis in pediatric patients from the multicentric ALLIC-GATLA-2010 clinical protocol in Argentina. By combining multiple bioinformatic tools, we successfully identified single nucleotide variants, fusion transcripts and gene expression profiles, achieving molecular classification of more than 90% of patients. We could also detect high-risk molecular features and novel genetic alterations. Results obtained in this work could be of clinical utility to improve risk stratification and identify therapeutic targets, especially in patients that currently result unclassified by traditional diagnostic techniques.

儿童急性淋巴细胞白血病（pediatric acute lymphoblastic leukemia, ALL）在分子层面呈现高度异质性，目前在B细胞型急性淋巴细胞白血病（B-ALL）中已鉴定出20余种分子亚型，这些亚型是风险适应性治疗与精准医学的核心依据。此类亚型以特异性染色体易位、基因表达谱、非整倍体与点突变为特征，其鉴定依赖于各中心的技术可及性。在此背景下，分子分型的日益复杂带来了技术、分析与经济层面的多重挑战，共同制约了其临床推广，尤其在中低收入国家。本研究针对阿根廷多中心ALLIC-GATLA-2010临床方案入组的初诊儿童B-ALL患者，采用转录组测序技术开展分子分型工作。通过整合多款生物信息学工具，本研究成功鉴定出单核苷酸变异、融合转录本与基因表达谱，实现了超过90%患者的分子分型。本研究还可检测高危分子特征与新型遗传变异。本研究所得结果可用于优化风险分层、筛选治疗靶点，尤其适用于当前传统诊断技术无法完成分型的患者。