AUTHOR=Wang Han , Cui Bowen , Sun Huiying , Zhang Fang , Rao Jianan , Wang Ronghua , Zhao Shuang , Shen Shuhong , Liu Yu 

TITLE=Aberrant GATA2 Activation in Pediatric B-Cell Acute Lymphoblastic Leukemia

JOURNAL=Frontiers in Pediatrics

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2021.795529

DOI=10.3389/fped.2021.795529

ISSN=2296-2360

ABSTRACT=<p><italic>GATA2</italic> 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, <italic>GATA2</italic> expression is restricted to HSCs and hematopoietic progenitors as well as early erythroid cells and megakaryocytic cells. Here we identified aberrant <italic>GATA2</italic> expression in B-cell acute lymphoblastic leukemia (B-ALL) by analyzing transcriptome sequencing data obtained from St. Jude Cloud. Differentially expressed genes upon <italic>GATA2</italic> activation showed significantly myeloid-like transcription signature. Further analysis identified several tumor-associated genes as targets of <italic>GATA2</italic> activation including <italic>BAG3</italic> and <italic>EPOR</italic>. In addition, the correlation between <italic>KMT2A-USP2</italic> fusion and <italic>GATA2</italic> activation not only indicates a potential trans-activating mechanism of <italic>GATA2</italic> but also suggests that <italic>GATA2</italic> is a target of KMT2A-USP2. Furthermore, by integrating whole-genome and transcriptome sequencing data, we showed that <italic>GATA2</italic> is also cis activated. A somatic focal deletion located in the <italic>GATA2</italic> neighborhood that disrupts the boundaries of topologically associating domains was identified in one B-ALL patient with <italic>GATA2</italic> activation. These evidences support the hypothesis that <italic>GATA2</italic> could be involved in leukemogenesis of B-ALL and can be transcriptionally activated through multiple mechanisms. The findings of aberrant activation of <italic>GATA2</italic> and its molecular function extend our understanding of transcriptional factor dysregulation in B-ALL.</p>