Department of Hematology, The First Hospital of Lanzhou University, Lanzhou, Gansu Province, China.
Biosci Rep. 2020 May 29;40(5). doi: 10.1042/BSR20200514.
Rearrangements involving the mixed lineage leukemia (MLL) gene are common adverse prognostic factors of pediatric acute lymphoblastic leukemia (ALL). Even allogeneic hematopoietic stem cell transplantation does not improve the outcome of ALL cases with some types of MLL rearrangements. The aim of the present study was to identify the co-expressed genes that related to MLL rearrangement (MLL-r) and elucidate the potential mechanisms of how MLL-r and their partner genes lead to leukemogenesis. Gene co-expression networks were constructed using the gene expression data and sample traits of 204 pretreated pediatric ALL patients, and co-expression modules significantly related to the MLL-r were screened out. Gene ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis of the module genes were performed. Hub genes were identified and their expression levels were analyzed in samples with or without MLL-r and the results were validated by an independent investigation. Furthermore, the relationships between the hub genes and sample traits were analyzed. In total, 21 co-expression modules were identified. The green module was positively correlated with MLL-r. PROM1, LGALS1, CD44, FUT4 and HOXA10 were identified as hub genes, which were involved in focal adhesion, calcium-dependent phospholipid binding, connective tissue development and transcriptional misregulation in cancer. The expression levels of the five hub genes were significantly increased in MLL-r samples, and the results were further validated. PROM1, LGALS1, CD44 and HOXA10 were positively related to the leukocyte count. These findings might provide novel insight regarding the mechanisms and potential therapeutic targets for pediatric ALL with MLL-r.
涉及混合谱系白血病（MLL）基因重排是儿童急性淋巴细胞白血病（ALL）的常见不良预后因素。即使进行同种异体造血干细胞移植，也不能改善某些类型 MLL 重排的 ALL 病例的预后。本研究旨在鉴定与 MLL 重排（MLL-r）相关的共表达基因，并阐明 MLL-r 及其伙伴基因导致白血病发生的潜在机制。使用 204 例预处理儿童 ALL 患者的基因表达数据和样本特征构建基因共表达网络，并筛选出与 MLL-r 显著相关的共表达模块。对模块基因进行基因本体注释和京都基因与基因组百科全书通路分析。鉴定枢纽基因，并分析有无 MLL-r 的样本中的表达水平，并通过独立研究进行验证。此外，还分析了枢纽基因与样本特征之间的关系。共鉴定出 21 个共表达模块。绿色模块与 MLL-r 呈正相关。鉴定出 PROM1、LGALS1、CD44、FUT4 和 HOXA10 为枢纽基因，它们参与了粘着斑、钙依赖性磷脂结合、结缔组织发育和癌症中的转录失调。在 MLL-r 样本中，这五个枢纽基因的表达水平显著升高，结果进一步得到验证。PROM1、LGALS1、CD44 和 HOXA10 与白细胞计数呈正相关。这些发现可能为具有 MLL-r 的儿童 ALL 的机制和潜在治疗靶点提供新的见解。
