PMID- 36464324
OWN - NLM
STAT- MEDLINE
DCOM- 20230307
LR  - 20230314
IS  - 1365-2141 (Electronic)
IS  - 0007-1048 (Linking)
VI  - 200
IP  - 6
DP  - 2023 Mar
TI  - The nuclear factor erythroid 2-related factor 2 agonist tert-butylhydroquinone 
      improves bone marrow mesenchymal stromal cell function in prolonged isolated 
      thrombocytopenia after allogeneic haematopoietic stem cell transplantation.
PG  - 759-768
LID - 10.1111/bjh.18585 [doi]
AB  - Prolonged isolated thrombocytopenia (PT) is a life-threatening comorbidity 
      associated with allogeneic haematopoietic stem cell transplantation (allo-HSCT). 
      Our previous study indicated that dysfunctional bone marrow mesenchymal stromal 
      cells (BM MSCs) played a role in PT pathogenesis and that reactive oxygen species 
      (ROS) accumulation was related to BM MSC senescence and apoptosis. However, the 
      mechanism of the increase in ROS levels in the BM MSCs of PT patients is unknown. 
      In the current case-control study, we investigated whether nuclear factor 
      erythroid 2-related factor 2 (NRF2), which is a central regulator of the cellular 
      anti-oxidant response that can clear ROS in human BM MSCs, was associated with PT 
      after allo-HSCT. We evaluated whether an NRF2 agonist (tert-butylhydroquinone, 
      TBHQ) could enhance BM MSCs from PT patients in vitro. We found that BM MSCs from 
      PT patients exhibited increased ROS levels and reduced NRF2 expression. 
      Multivariate analysis showed that low NRF2 expression was an independent risk 
      factor for primary PT [p = 0.032, Odds ratio (OR) 0.868, 95% confidence interval 
      (CI) 0.764-0.988]. In-vitro treatment with TBHQ improved the quantity and 
      function of BM MSCs from PT patients by downregulating ROS levels and rescued the 
      impaired BM MSC support of megakaryocytopoiesis. In conclusion, these results 
      suggested that NRF2 downregulation in human BM MSCs might be involved in the 
      pathogenesis of PT after allo-HSCT and that BM MSC impairment could be improved 
      by NRF2 agonist in vitro. Although further validation is needed, our data 
      indicate that NRF2 agonists might be a potential therapeutic approach for PT 
      patients after allo-HSCT.
CI  - (c) 2022 British Society for Haematology and John Wiley & Sons Ltd.
FAU - Luo, Xue-Yi
AU  - Luo XY
AUID- ORCID: 0000-0001-5835-8310
AD  - National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory 
      of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital, 
      Peking University Institute of Hematology, Beijing, China.
FAU - Kong, Yuan
AU  - Kong Y
AUID- ORCID: 0000-0001-5594-2642
AD  - National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory 
      of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital, 
      Peking University Institute of Hematology, Beijing, China.
FAU - Lv, Meng
AU  - Lv M
AUID- ORCID: 0000-0001-6625-9523
AD  - National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory 
      of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital, 
      Peking University Institute of Hematology, Beijing, China.
FAU - Mo, Xiao-Dong
AU  - Mo XD
AUID- ORCID: 0000-0002-9881-7945
AD  - National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory 
      of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital, 
      Peking University Institute of Hematology, Beijing, China.
FAU - Wang, Yu
AU  - Wang Y
AUID- ORCID: 0000-0003-1253-7465
AD  - National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory 
      of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital, 
      Peking University Institute of Hematology, Beijing, China.
AD  - Peking-Tsinghua Center for Life Sciences, Beijing, China.
FAU - Xu, Lan-Ping
AU  - Xu LP
AUID- ORCID: 0000-0002-0267-1081
AD  - National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory 
      of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital, 
      Peking University Institute of Hematology, Beijing, China.
FAU - Zhang, Xiao-Hui
AU  - Zhang XH
AUID- ORCID: 0000-0003-0245-6792
AD  - National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory 
      of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital, 
      Peking University Institute of Hematology, Beijing, China.
FAU - Huang, Xiao-Jun
AU  - Huang XJ
AUID- ORCID: 0000-0002-2145-6643
AD  - National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory 
      of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital, 
      Peking University Institute of Hematology, Beijing, China.
AD  - Peking-Tsinghua Center for Life Sciences, Beijing, China.
FAU - Tang, Fei-Fei
AU  - Tang FF
AUID- ORCID: 0000-0003-0460-9887
AD  - National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory 
      of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital, 
      Peking University Institute of Hematology, Beijing, China.
LA  - eng
GR  - 2021YFC2500302/National Key Research and Development Program of China/
GR  - 81900178/National Natural Science Foundation of China/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221204
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - C12674942B (2-tert-butylhydroquinone)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (NF-E2-Related Factor 2)
SB  - IM
MH  - Humans
MH  - Bone Marrow/pathology
MH  - Case-Control Studies
MH  - Reactive Oxygen Species/metabolism
MH  - NF-E2-Related Factor 2/metabolism
MH  - Transplantation, Homologous/adverse effects
MH  - *Hematopoietic Stem Cell Transplantation/adverse effects
MH  - Bone Marrow Cells/pathology
MH  - *Thrombocytopenia/etiology
MH  - *Mesenchymal Stem Cells/metabolism
MH  - *Mesenchymal Stem Cell Transplantation/adverse effects
OTO - NOTNLM
OT  - allogeneic haematopoietic stem cell transplantation
OT  - mesenchymal stem cell
OT  - nuclear factor erythroid 2-related factor 2
OT  - prolonged isolated thrombocytopenia
OT  - tert-butylhydroquinone
EDAT- 2022/12/05 06:00
MHDA- 2023/03/08 06:00
CRDT- 2022/12/04 20:52
PHST- 2022/11/11 00:00 [revised]
PHST- 2022/09/17 00:00 [received]
PHST- 2022/11/21 00:00 [accepted]
PHST- 2022/12/05 06:00 [pubmed]
PHST- 2023/03/08 06:00 [medline]
PHST- 2022/12/04 20:52 [entrez]
AID - 10.1111/bjh.18585 [doi]
PST - ppublish
SO  - Br J Haematol. 2023 Mar;200(6):759-768. doi: 10.1111/bjh.18585. Epub 2022 Dec 4.