Effect of SCARI1 in progression of JAK2V617F mutant myeloproliferative neoplasms

HU Xin; WEI Xiao-jing; ZHANG Yu-hui; MA Jin-yu; DUAN Yi-fan; SHANG Ke; TENG Guang-shuai; WANG Yan; DU Chen-xiao; ZHANG Hui-qin; YUAN Wei-ping; SHAO Zong-hong; BAI Jie

doi:10.19538/j.nk2025040108

Abstract：Objective To investigate the role of SCARI1 in the progression of JAK2V617F mutated MPN to myelofibrosis.Methods Bone marrow CD34+cells of MPN(n=12),sMF(n=12)and sAML(n=7)patients with JAK2V617F mutation from Dec.2022 to Dec.2024 in Tianjin Medical University Second Hospital were analyzed by RNA-seq,and the differential genes were analyzed by bioinformatics.RT-qPCR and flow cytometry were used to detect the expression of SCARI1 gene and its protein in CD34+primary bone marrow cells of MPN patients.HEL cells with SCARI1 overexpression was constructed,and the morphological changes of HEL cells in the overexpression group were analyzed after staining.Cell proliferation was detected by CCK-8,cell cycle,apoptosis and differentiation into megakaryocytes induced by PMA were detected by flow cytometry.Results RNA-seq,RT-qPCR and flow cytometry results showed that the expression level of SCARI1 gene and protein was significantly increased in CD34+hematopoietic stem cells of sMF patients(P＜0.05),and was verified in the database(GSE174060).Compared with vehicle group and wild type group,the proportion of abnormal morphology of HEL cells increased significantly after SCARI1 overexpression,and the proliferation of HEL cells with SCARI1 overexpression was faster.The proportion of S and G2/M phase of HEL cells in the overexpression group increased,and the proportion of G0/G1 phase cells decreased.The number of differentiation of HEL cells into megakaryocytes in PMA-induced overexpression group was significantly increased,all the differences were statistically significant(all P＜0.05).Conclusion SCARI1 is significantly increased in CD34+hematopoietic stem cells in sMF patients.SCARI1 may play a role in promoting the progression of JAK2V617F mutated MPN to sMF disease by inducing HEL cells to differentiate into megakaryocytes.