Aberrant GATA2 Activation in Pediatric B-Cell Acute Lymphoblastic Leukemia

• Published in: Frontiers in pediatrics 2022-01, Vol.9, p.795529-795529
• Main Authors: Wang, Han, Cui, Bowen, Sun, Huiying, Zhang, Fang, Rao, Jianan, Wang, Ronghua, Zhao, Shuang, Shen, Shuhong, Liu, Yu
• Format: Article
• Language: English
• Subjects: cis-activation; GATA2; leukemogenesis; pediatric B-cell acute lymphoblastic leukemia; Pediatrics; transcriptional dysregulation
• ISSN: 2296-2360; 2296-2360
• DOI: 10.3389/fped.2021.795529

is a transcription factor that is critical for the generation and survival of hematopoietic stem cells (HSCs). It also plays an important role in the regulation of myeloid differentiation. Accordingly, expression is restricted to HSCs and hematopoietic progenitors as well as early erythroid cells and megakaryocytic cells. Here we identified aberrant expression in B-cell acute lymphoblastic leukemia (B-ALL) by analyzing transcriptome sequencing data obtained from St. Jude Cloud. Differentially expressed genes upon activation showed significantly myeloid-like transcription signature. Further analysis identified several tumor-associated genes as targets of activation including and . In addition, the correlation between fusion and activation not only indicates a potential trans-activating mechanism of but also suggests that is a target of KMT2A-USP2. Furthermore, by integrating whole-genome and transcriptome sequencing data, we showed that is also cis activated. A somatic focal deletion located in the neighborhood that disrupts the boundaries of topologically associating domains was identified in one B-ALL patient with activation. These evidences support the hypothesis that could be involved in leukemogenesis of B-ALL and can be transcriptionally activated through multiple mechanisms. The findings of aberrant activation of and its molecular function extend our understanding of transcriptional factor dysregulation in B-ALL.