miR-155 is associated with the leukemogenic potential of the class IV granulocyte colony-stimulating factor receptor in CD34⁺ progenitor cells

Molecular Medicine
HaiJiao ZhangConstança Figueiredo

Abstract

Granulocyte colony-stimulating factor (G-CSF) is a major regulator of granulopoiesis on engagement with the G-CSF receptor (G-CSFR). The truncated, alternatively spliced, class IV G-CSFR (G-CSFRIV) has been associated with defective differentiation and relapse risk in pediatric acute myeloid leukemia (AML) patients. However, the detailed biological properties of G-CSFRIV in human CD34(+) hematopoietic stem and progenitor cells (HSPCs) and the potential leukemogenic mechanism of this receptor remain poorly understood. In the present study, we observed that G-CSFRIV-overexpressing (G-CSFRIV(+)) HSPCs demonstrated an enhanced proliferative and survival capacity on G-CSF stimulation. Cell cycle analyses showed a higher frequency of G-CSFRIV(+) cells in the S and G2/M phase. Also, apoptosis rates were significantly lower in G-CSFRIV(+) HSPCs. These findings were shown to be associated with a sustained Stat5 activation and elevated miR-155 expression. In addition, G-CSF showed to further induce G-CSFRIV and miR-155 expression of peripheral blood mononuclear cells isolated from AML patients. A Stat5 pharmacological inhibitor or ribonucleic acid (RNA) interference-mediated silencing of the expression of miR-155 abrogated the aberrant p...Continue Reading

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Citations

Sep 7, 2018·Leukemia & Lymphoma·Chengcheng HeXiaoli Zheng
Oct 6, 2016·Oncotarget·Qiong LiaoGuosheng Jiang
Oct 28, 2019·International Journal of Molecular Sciences·Anjana AjikumarJulie E Simpson
Dec 10, 2019·Cytokine·Borwyn Wang, Hrishikesh Mehta
Aug 7, 2021·Biology·Mateusz NowickiAnna Szmigielska-Kapłon

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