AUTHOR=Zhang Jubin , Qi Lijuan , Wang Tanzhen , An Jingnan , Zhou Biqi , Fang Yanglan , Liu Yujie , Shan Meng , Hong Dengli , Wu Depei , Xu Yang , Liu Tianhui 

TITLE=FEV Maintains Homing and Expansion by Activating ITGA4 Transcription in Primary and Relapsed AML

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.890346

DOI=10.3389/fonc.2022.890346

ISSN=2234-943X

ABSTRACT=<p>Acute myeloid leukemia (AML) is an aggressive hematological malignancy that recurs in approximately 50% of cases. Elevated homing and uncontrolled expansion are characteristics of AML cells. Here, we identified that Fifth Ewing Variant (FEV) regulates the homing and expansion of AML cells. We found that <italic>FEV</italic> was re-expressed in 30% of primary AML samples and in almost all relapsed AML samples, and <italic>FEV</italic> expression levels were significantly higher in relapsed samples compared to primary samples. Interference of <italic>FEV</italic> expression in AML cell lines delayed leukemic progression and suppressed homing and proliferation. Moreover, FEV directly activated integrin subunit alpha 4 (<italic>ITGA4</italic>) transcription in a dose-dependent manner. Inhibition of integrin α4 activity with natalizumab (NZM) reduced the migration and colony-forming abilities of blasts and leukemic-initiating cells (LICs) in both primary and relapsed AML. Thus, our study suggested that FEV maintains the homing and expansion of AML cells by activating <italic>ITGA4</italic> transcription and that targeting <italic>ITGA4</italic> inhibits the colony-forming and migration capacities of blasts and LICs. Thus, these findings suggested that the <italic>FEV</italic>-<italic>ITGA4</italic> axis may be a therapeutic target for both primary and relapsed AML.</p>