The Journal of Practical Medicine >

2025 , Vol. 41 >Issue 2: 294 - 299

DOI: https://doi.org/10.3969/j.issn.1006-5725.2025.02.021

Reviews

Research advances of mesenchymal stem cells in the bone marrow microenvironment of acute myeloid leukemia

  • Xingyu WAN ,
  • Nan LI ,
  • Shuiqing LIU ,
  • Xi. ZHANG
Expand
  • *.Medical Center of Hematology，Chongqing Key Laboratory of Hematology and Microenvironment，Second Affiliated Hospital of Army Medical University，Chongqing 400037，Chongqing，China

Received date: 2024-10-24

  Online published: 2025-01-26

Fold

Abstract

Acute myeloid leukemia （AML） is a highly heterogeneous hematological malignancy， driven by multiple gene mutations and characterized by high incidence and mortality rates. Mesenchymal stem cells （MSCs）， which possess self?renewal and multidirectional differentiation potentials， play crucial roles within the bone marrow microenvironment. Emerging research has demonstrated that MSCs contribute to AML development through various mechanisms， including mitochondrial transfer， transmission of extracellular vesicles， adipogenic differentiation， and secretion of pro?cancer proteins. This review provides a comprehensive summary of the involvement of MSCs in the AML bone marrow microenvironment and offers insights for developing novel therapeutic strategies targeting MSCs in AML treatment.

Key words： acute myeloid leukemia; mesenchymal stem cell; bone marrow microenvironment; cancer-promoting effect; targeted therapy

Cite this article

Xingyu WAN , Nan LI , Shuiqing LIU , Xi. ZHANG . Research advances of mesenchymal stem cells in the bone marrow microenvironment of acute myeloid leukemia[J]. The Journal of Practical Medicine, 2025 , 41(2) : 294 -299 . DOI: 10.3969/j.issn.1006-5725.2025.02.021

References

1 WANG Y， CHANG Y J， CHEN J， et al. Consensus on the monitoring， treatment， and prevention of leukaemia relapse after allogeneic haematopoietic stem cell transplantation in China： 2024 update［J］. Cancer Lett， 2024， 605： 217264. doi:10.1016/j.canlet.2024.217264
2 WANG X， HUANG R， WU W， et al. Amplifying STING activation by bioinspired nanomedicine for targeted chemo- and immunotherapy of acute myeloid leukemia［J］. Acta Biomaterialia， 2023， 157： 381-394. doi:10.1016/j.actbio.2022.11.007
3 KANDARAKOV O， BELYAVSKY A， SEMENOVA E. Bone Marrow Niches of Hematopoietic Stem and Progenitor Cells［J］. Int J Mol Sci， 2022， 23（8）： 4462. doi:10.3390/ijms23084462
4 WANG Y， FANG J， LIU B， et al. Reciprocal regulation of mesenchymal stem cells and immune responses［J］. Cell Stem Cell， 2022， 29（11）： 1515-1530. doi:10.1016/j.stem.2022.10.001
5 FAN S， SUN X， SU C， et al. Macrophages-bone marrow mesenchymal stem cells crosstalk in bone healing［J］. Front Cell Dev Biol， 2023， 11： 1193765. doi:10.3389/fcell.2023.1193765
6 FORTE D， GARCíA-FERNáNDEZ M， SáNCHEZ-AGUILERA A， et al. Bone Marrow Mesenchymal Stem Cells Support Acute Myeloid Leukemia Bioenergetics and Enhance Antioxidant Defense and Escape from Chemotherapy［J］. Cell Metab， 2020， 32（5）： 829-843.e829. doi:10.1016/j.cmet.2020.09.001
7 MOSCHOI R， IMBERT V， NEBOUT M， et al. Protective mitochondrial transfer from bone marrow stromal cells to acute myeloid leukemic cells during chemotherapy［J］. Blood， 2016， 128（2）： 253-264. doi:10.1182/blood-2015-07-655860
8 MARLEIN C R， ZAITSEVA L， PIDDOCK R E， et al. NADPH oxidase-2 derived superoxide drives mitochondrial transfer from bone marrow stromal cells to leukemic blasts［J］. Blood， 2017， 130（14）： 1649-1660. doi:10.1182/blood-2017-03-772939
9 SAITO K， ZHANG Q， YANG H， et al. Exogenous mitochondrial transfer and endogenous mitochondrial fission facilitate AML resistance to OxPhos inhibition［J］. Blood Adv， 2021， 5（20）： 4233-4255.
10 YOU R， WANG B， CHEN P， et al. Metformin sensitizes AML cells to chemotherapy through blocking mitochondrial transfer from stromal cells to AML cells［J］. Cancer Lett， 2022， 532： 215582. doi:10.1016/j.canlet.2022.215582
11 MISTRY J J， MOORE J A， KUMAR P， et al. Daratumumab inhibits acute myeloid leukaemia metabolic capacity by blocking mitochondrial transfer from mesenchymal stromal cells［J］. Haematologica， 2021， 106（2）： 589-592. doi:10.3324/haematol.2019.242974
12 MENDES M， MONTEIRO A C， NETO E， et al. Transforming the Niche： The Emerging Role of Extracellular Vesicles in Acute Myeloid Leukaemia Progression［J］. Int J Mol Sci， 2024， 25（8）： 4430. doi:10.3390/ijms25084430
13 WU J， ZHANG Y， LI X， et al. Exosomes from bone marrow mesenchymal stem cells decrease chemosensitivity of acute myeloid leukemia cells via delivering miR-10a［J］. Biochem Biophys Res Commun， 2022， 622： 149-156. doi:10.1016/j.bbrc.2022.07.017
14 JI D， HE Y， LU W， et al. Small-sized extracellular vesicles （EVs） derived from acute myeloid leukemia bone marrow mesenchymal stem cells transfer miR-26a-5p to promote acute myeloid leukemia cell proliferation， migration， and invasion［J］. Hum Cell， 2021， 34（3）： 965-976. doi:10.1007/s13577-021-00501-7
15 CHENG H， DING J， TANG G， et al. Human mesenchymal stem cells derived exosomes inhibit the growth of acute myeloid leukemia cells via regulating miR-23b-5p/TRIM14 pathway［J］. Mol Med， 2021， 27（1）： 128. doi:10.1186/s10020-021-00393-1
16 ZHANG F， LU Y， WANG M， et al. Exosomes derived from human bone marrow mesenchymal stem cells transfer miR-222-3p to suppress acute myeloid leukemia cell proliferation by targeting IRF2/INPP4B［J］. Mol Cell Probes， 2020， 51： 101513. doi:10.1016/j.mcp.2020.101513
17 XU Y C， LIN Y S， ZHANG L， et al. MicroRNAs of bone marrow mesenchymal stem cell-derived exosomes regulate acute myeloid leukemia cell proliferation and apoptosis［J］. Chin Med J （Engl）， 2020， 133（23）： 2829-2839. doi:10.1097/cm9.0000000000001138
18 SUN L， YANG N， CHEN B， et al. A novel mesenchymal stem cell-based regimen for acute myeloid leukemia differentiation therapy［J］. Acta Pharm Sin B， 2023， 13（7）： 3027-3042. doi:10.1016/j.apsb.2023.05.007
19 SHAFAT M S， OELLERICH T， MOHR S， et al. Leukemic blasts program bone marrow adipocytes to generate a protumoral microenvironment［J］. Blood， 2017， 129（10）： 1320-1332. doi:10.1182/blood-2016-08-734798
20 YE H， ADANE B， KHAN N， et al. Leukemic Stem Cells Evade Chemotherapy by Metabolic Adaptation to an Adipose Tissue Niche［J］. Cell Stem Cell， 2016， 19（1）： 23-37. doi:10.1016/j.stem.2016.06.001
21 YANG S， LU W， ZHAO C， et al. Leukemia cells remodel marrow adipocytes via TRPV4-dependent lipolysis［J］. Haematologica， 2020， 105（11）： 2572-2583. doi:10.3324/haematol.2019.225763
22 LIAO X， CAI D， LIU J， et al. Deletion of Mettl3 in mesenchymal stem cells promotes acute myeloid leukemia resistance to chemotherapy［J］. Cell Death Dis， 2023， 14（12）： 796. doi:10.1038/s41419-023-06325-7
23 AZADNIV M， MYERS J R， MCMURRAY H R， et al. Bone marrow mesenchymal stromal cells from acute myelogenous leukemia patients demonstrate adipogenic differentiation propensity with implications for leukemia cell support［J］. Leukemia， 2020， 34（2）： 391-403. doi:10.1038/s41375-019-0568-8
24 ?BACKA H， MASONI S， POLI G， et al. SMS121， a new inhibitor of CD36， impairs fatty acid uptake and viability of acute myeloid leukemia［J］. Sci Rep， 2024， 14（1）： 9104. doi:10.1038/s41598-024-58689-1
25 DE FREITAS F A， LEVY D， REICHERT C O， et al. Influence of Human Bone Marrow Mesenchymal Stem Cells Secretome from Acute Myeloid Leukemia Patients on the Proliferation and Death of K562 and K562-Lucena Leukemia Cell Lineages［J］. Int J Mol Sci， 2024， 25（9）： 4748. doi:10.3390/ijms25094748
26 LU J， DONG Q， ZHANG S， et al. Acute myeloid leukemia （AML）-derived mesenchymal stem cells induce chemoresistance and epithelial-mesenchymal transition-like program in AML through IL-6/JAK2/STAT3 signaling［J］. Cancer Sci， 2023， 114（8）： 3287-3300. doi:10.1111/cas.15855
27 ZHANG Y， GUO H， ZHANG Z， et al. IL-6 promotes chemoresistance via upregulating CD36 mediated fatty acids uptake in acute myeloid leukemia［J］. Exp Cell Res， 2022， 415（1）： 113112. doi:10.1016/j.yexcr.2022.113112
28 HOU D， WANG B， YOU R， et al. Stromal cells promote chemoresistance of acute myeloid leukemia cells via activation of the IL-6/STAT3/OXPHOS axis［J］. Ann Transl Med， 2020， 8（21）： 1346. doi:10.21037/atm-20-3191
29 ANDERSON N R， SHETH V， LI H， et al. Microenvironmental CXCL12 deletion enhances Flt3-ITD acute myeloid leukemia stem cell response to therapy by reducing p38 MAPK signaling［J］. Leukemia， 2023， 37（3）： 560-570. doi:10.1038/s41375-022-01798-5
30 VI?ADO A C， CALVO I A， CENZANO I， et al. The bone marrow niche regulates redox and energy balance in MLL： AF9 leukemia stem cells［J］. Leukemia， 2022， 36（8）： 1969-1979. doi:10.1038/s41375-022-01601-5
31 YEHUDAI-RESHEFF S， ATTIAS-TURGEMAN S， SABBAH R， et al. Abnormal morphological and functional nature of bone marrow stromal cells provides preferential support for survival of acute myeloid leukemia cells［J］. Int J Cancer， 2019， 144（9）： 2279-2289. doi:10.1002/ijc.32063
32 MODAK R V， DE OLIVEIRA REBOLA K G， MCCLATCHY J， et al. Targeting CCL2/CCR2 Signaling Overcomes MEK Inhibitor Resistance in Acute Myeloid Leukemia［J］. Clin Cancer Res， 2024， 30（10）： 2245-2259. doi:10.1158/1078-0432.ccr-23-2654
33 AASEB? E， BRENNER A K， HERNANDEZ-VALLADARES M， et al. Patient Heterogeneity in Acute Myeloid Leukemia： Leukemic Cell Communication by Release of Soluble Mediators and Its Effects on Mesenchymal Stem Cells［J］. Diseases， 2021， 9（4）： 74. doi:10.3390/diseases9040074
34 LI H， WANG Y， YANG F， et al. Clonal MDS/AML cells with enhanced TWIST1 expression reprogram the differentiation of bone marrow MSCs［J］. Redox Biol， 2023， 67： 102900. doi:10.1016/j.redox.2023.102900
35 KARGAR-SICHANI Y， MOHAMMADI M H， AMIRI V， et al. Effect of Acute Myeloid Leukemia-derived Extracellular Vesicles on Bone Marrow Mesenchymal Stromal Cells： Expression of Poor Prognosis Genes［J］. Arch Med Res， 2023， 54（2）： 95-104. doi:10.1016/j.arcmed.2022.12.008
36 ZHANG L， ZHAO Q， CANG H， et al. Acute Myeloid Leukemia Cells Educate Mesenchymal Stromal Cells toward an Adipogenic Differentiation Propensity with Leukemia Promotion Capabilities［J］. Adv Sci （Weinh）， 2022， 9（16）： 2105811. doi:10.1002/advs.202270101
37 WACLAWICZEK A， HAMILTON A， ROUAULT-PIERRE K， et al. Mesenchymal niche remodeling impairs hematopoiesis via stanniocalcin 1 in acute myeloid leukemia［J］. J Clin Invest， 2020， 130（6）： 3038-3050. doi:10.1172/jci133187
38 SCHELKER R C， KRATZER A， MüLLER G， et al. Stanniocalcin 1 is overexpressed in multipotent mesenchymal stromal cells from acute myeloid leukemia patients［J］. Hematology， 2021， 26（1）： 565-576. doi:10.1080/16078454.2021.1962048
39 CHANDRAN P， LE Y， LI Y， et al. Mesenchymal stromal cells from patients with acute myeloid leukemia have altered capacity to expand differentiated hematopoietic progenitors［J］. Leuk Res， 2015， 39（4）： 486-493. doi:10.1016/j.leukres.2015.01.013
40 HORIGUCHI H， KOBUNE M， KIKUCHI S， et al. Extracellular vesicle miR-7977 is involved in hematopoietic dysfunction of mesenchymal stromal cells via poly（rC） binding protein 1 reduction in myeloid neoplasms［J］. Haematologica， 2016， 101（4）： 437-447. doi:10.3324/haematol.2015.134932
41 LAMBLE A J， LIND E F. Targeting the Immune Microenvironment in Acute Myeloid Leukemia： A Focus on T Cell Immunity［J］. Front Oncol， 2018， 8： 213. doi:10.3389/fonc.2018.00213
42 WU L， LIN Q， MA Z， et al. Mesenchymal PGD（2） activates an ILC2-Treg axis to promote proliferation of normal and malignant HSPCs［J］. Leukemia， 2020， 34（11）： 3028-3041. doi:10.1038/s41375-020-0843-8
43 MANSOUR I， ZAYED R A， SAID F， et al. Indoleamine 2，3-dioxygenase and regulatory T cells in acute myeloid leukemia［J］. Hematology， 2016， 21（8）： 447-453. doi:10.1080/10245332.2015.1106814
44 CORRADI G， BASSANI B， SIMONETTI G， et al. Release of IFNγ by Acute Myeloid Leukemia Cells Remodels Bone Marrow Immune Microenvironment by Inducing Regulatory T Cells［J］. Clin Cancer Res， 2022， 28（14）： 3141-3155. doi:10.1158/1078-0432.ccr-21-3594
45 FERRELL P B， KORDASTI S. Hostile Takeover： Tregs Expand in IFNγ-Rich AML Microenvironment［J］. Clin Cancer Res， 2022， 28（14）： 2986-2988. doi:10.1158/1078-0432.ccr-22-1030
46 BORELLA G， DA ROS A， BORILE G， et al. Targeting the plasticity of mesenchymal stromal cells to reroute the course of acute myeloid leukemia［J］. Blood， 2021， 138（7）： 557-570.
47 侯勇哲， 张琴， 赵霄晨， 等. 间充质干细胞来源的胞外囊泡在急性肺损伤治疗中的研究进展［J］. 实用医学杂志， 2023， 39（3）： 390-394. doi:10.3969/j.issn.1006-5725.2023.03.023
48 YANG A， WANG X， JIN L，et al. Human umbilical cord mesenchymal stem cell exosomes deliver potent oncolytic reovirus to acute myeloid leukemia cells［J］. Virology， 2024， 598： 110171. doi:10.1016/j.virol.2024.110171
49 WEN J， CHEN Y， LIAO C， et al. Engineered mesenchymal stem cell exosomes loaded with miR-34c-5p selectively promote eradication of acute myeloid leukemia stem cells［J］. Cancer Lett， 2023， 575： 216407. doi:10.1016/j.canlet.2023.216407
50 万星煜， 郭焕平， 黄瑞昊， 等. ADAR1介导的RNA编辑在血液肿瘤中的调控作用［J］. 生物化学与生物物理进展， 2024， 51（2）： 300-308.
51 游静茹， 杨璐， 崔小丽， 等. 急性髓系白血病中表观遗传学异常的研究进展［J］. 实用医学杂志， 2023， 39（10）： 1316-1319.
Options
Outlines

/

〈 〉