美国圣裘德儿童研究医院Jeffery M. Klco团队表明，一个新基因组框架可对小儿急性髓性白血病进行分类。相关论文于2024年1月11日在线发表在《自然—遗传学》杂志上。

为了全面界定小儿急性髓性白血病（pAML）的基因组图谱，研究人员将887例pAML系统地分为23个互不相同的分子类别，包括UBTF或BCL11B等新的主要实体，覆盖了队列中 91.4% 的患者。这些分子类别与独特的表达谱和突变模式相关。例如，以特定的HOXA或HOXB表达特征为特征的分子类别显示了RAS通路基因、FLT3或WT1的不同突变模式，这表明它们具有共同的生物学机制。

研究人员利用两个独立的队列研究表明，分子类别与临床结果密切相关，从而根据这些更新的分子类别和最小残留病建立了新的pAML预后框架。这一全面的诊断和预后框架共同构成了未来pAML分类和治疗策略的基础。

研究人员表示，最近对pAML的研究揭示了小儿特异性驱动基因改变，其中许多改变在目前的分类模式中代表性不足。

附：英文原文

Title: A new genomic framework to categorize pediatric acute myeloid leukemia

Author: Umeda, Masayuki, Ma, Jing, Westover, Tamara, Ni, Yonghui, Song, Guangchun, Maciaszek, Jamie L., Rusch, Michael, Rahbarinia, Delaram, Foy, Scott, Huang, Benjamin J., Walsh, Michael P., Kumar, Priyadarshini, Liu, Yanling, Yang, Wenjian, Fan, Yiping, Wu, Gang, Baker, Sharyn D., Ma, Xiaotu, Wang, Lu, Alonzo, Todd A., Rubnitz, Jeffrey E., Pounds, Stanley, Klco, Jeffery M.

Issue&Volume: 2024-01-11

Abstract: Recent studies on pediatric acute myeloid leukemia (pAML) have revealed pediatric-specific driver alterations, many of which are underrepresented in the current classification schemas. To comprehensively define the genomic landscape of pAML, we systematically categorized 887 pAML into 23 mutually distinct molecular categories, including new major entities such as UBTF or BCL11B, covering 91.4% of the cohort. These molecular categories were associated with unique expression profiles and mutational patterns. For instance, molecular categories characterized by specific HOXA or HOXB expression signatures showed distinct mutation patterns of RAS pathway genes, FLT3 or WT1, suggesting shared biological mechanisms. We show that molecular categories were strongly associated with clinical outcomes using two independent cohorts, leading to the establishment of a new prognostic framework for pAML based on these updated molecular categories and minimal residual disease. Together, this comprehensive diagnostic and prognostic framework forms the basis for future classification of pAML and treatment strategies.

DOI: 10.1038/s41588-023-01640-3

Source: https://www.nature.com/articles/s41588-023-01640-3