Acute myeloid leukemia cells adhere to bone marrow and acquire chemoresistance by downregulating UNC5B expression

Teng Teng; Liping Ren; Jilong Xiao; Zhiyu Shi; Lanbo Li; Chunhong Song

doi:10.3389/fonc.2024.1394443

Acute myeloid leukemia cells adhere to bone marrow and acquire chemoresistance by downregulating UNC5B expression

Front Oncol. 2024 Sep 24:14:1394443. doi: 10.3389/fonc.2024.1394443. eCollection 2024.

Authors

Teng Teng^#¹, Liping Ren^#², Jilong Xiao³, Zhiyu Shi⁴, Lanbo Li⁵, Chunhong Song¹

Affiliations

¹ Shandong Key Laboratory of Traditional Chinese Medicine and Stress Injury, Department of Laboratory Animal Center, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
² Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China.
³ Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
⁴ Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
⁵ Laboratory Animal Center, Qilu Hospital, Shandong University, Jinan, Shandong, China.

^# Contributed equally.

Abstract

Acute myeloid leukemia (AML) is a malignant tumor of the hematological system. Because of its characteristics of recurrence, refractory and chemoresistance, new therapeutic targets need to be identified. Adhesion and proliferation are characteristics of AML cells, and critical steps in inducing chemotherapy resistance. In this study, we reported that UNC5B inhibits AML cell bone marrow adhesion, inhibits AML cell proliferation and increases sensitivity to chemotherapy. Mechanistically, RNA sequencing (RNA-seq) and experimental results revealed that overexpression of UNC5B inhibits adhesion and proliferation signaling pathways and inhibits the expression of MPZL1, CLDN23, IGF2 and WNT7B. In conclusion, our findings suggest that UNC5B serves as a prognostic indicator and a potential therapeutic target for AML.

Keywords: UNC5B; acute myeloid leukemia; adhesion; chemoresistance; proliferation.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Natural Science Foundation of Shandong Province (No. ZR2020MH341).