Open AccessHyperleukocytic Acute Leukemia Circulating Exosomes Regulate HSCs and BM-MSCs
Author(s) -
Yanmei Yang,
Haiping He,
Jigang He,
Xuezhong Gu,
Peng Hu,
Rongxia Zuo,
Yalian Sa
Publication year - 2021
Publication title -
journal of healthcare engineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.509
H-Index - 29
eISSN - 2040-2309
pISSN - 2040-2295
DOI - 10.1155/2021/9457070
Subject(s) - microvesicles , haematopoiesis , mesenchymal stem cell , downregulation and upregulation , bone marrow , stem cell , progenitor cell , exosome , immunology , microrna , cancer research , biology , microbiology and biotechnology , gene , biochemistry
Hyperleukocytic acute leukemia (HLAL) circulating exosomes are delivered to hematopoietic stem cells (HSCs) and bone marrow mesenchymal stem cells (BM-MSCs), thereby inhibiting the normal hematopoietic process. In this paper, we have evaluated and explored the effects of miR-125b, which is carried by HLAL-derived exosomes, on the hematopoietic function of HSCs and BM-MSCs. For this purpose, we have isolated exosomes from the peripheral blood of HLAL patients and healthy volunteers. Then, we measured the level of miR-125b in exosomes cocultured exosomes with HSCs and BM-MSCs. Moreover, we have used miR-125b inhibitors/mimic for intervention and then measured miR-125b expression and colony forming unit (CFU). Apart from it, HSC and BM-MSC hematopoietic-related factors α -globulin, γ -globulin, CSF2, CRTX4 and CXCL12, SCF, IGF1, and DKK1 expression were measured. Evaluation of the miR-125b and BAK1 targeting relationship, level of miR-125b, and expression of hematopoietic-related genes was performed after patients are treated with miR-125b mimic and si-BAK1. We have observed that miR-125b was upregulated in HLAL-derived exosomes. After HLAL-exosome acts on HSCs, the level of miR-125b is upregulated, reducing CFU and affecting the expression of α -globulin, γ -globulin, CSF2, and CRCX4. For BM-MSCs, after the action of HLAL-exo, the level of miR-125b is upregulated and affected the expression of CXCL12, SCF, IGF1, and DKK1. Exosomes derived from HLAL carry miR-125b to target and regulate BAK1. Further study confirmed that miR-125b and BAK1mimic reduced the expression of miR-125b and reversed the effect of miR-125b mimic on hematopoietic-related genes. These results demonstrated that HLAL-derived exosomes carrying miR-125b inhibit the hematopoietic differentiation of HSC and hematopoietic support function of BM-MSC through BAK1.