Single-cell transcriptomics dissects the transcriptome alterations of hematopoietic stem cells in myelodysplastic neoplasms.
Hematopoietic stem cells
Leukemic transformation
Myelodysplastic neoplasms
Transcriptome alterations
Journal
Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741
Informations de publication
Date de publication:
17 Apr 2024
17 Apr 2024
Historique:
received:
26
02
2024
accepted:
04
04
2024
medline:
19
4
2024
pubmed:
18
4
2024
entrez:
17
4
2024
Statut:
epublish
Résumé
Myelodysplastic neoplasms (MDS) are myeloid neoplasms characterized by disordered differentiation of hematopoietic stem cells and a predisposition to acute myeloid leukemia (AML). The underline pathogenesis remains unclear. In this study, the trajectory of differentiation and mechanisms of leukemic transformation were explored through bioinformatics analysis of single-cell RNA-Seq data from hematopoietic stem and progenitor cells (HSPCs) in MDS patients. Among the HSPC clusters, the proportion of common myeloid progenitor (CMP) was the main cell cluster in the patients with excess blasts (EB)/ secondary AML. Cell cycle analysis indicated the CMP of MDS patients were in an active proliferative state. The genes involved in the cell proliferation, such as MAML3 and PLCB1, were up-regulated in MDS CMP. Further validation analysis indicated that the expression levels of MAML3 and PLCB1 in patients with MDS-EB were significantly higher than those without EB. Patients with high expression of PLCB1 had a higher risk of transformation to AML. PLCB1 inhibitor can suppress proliferation, induce cell cycle arrest, and activate apoptosis of leukemic cells in vitro. This study revealed the transcriptomic change of HSPCs in MDS patients along the pseudotime and indicated that PLCB1 plays a key role in the transformation of MDS into leukemia.
Sections du résumé
BACKGROUND
BACKGROUND
Myelodysplastic neoplasms (MDS) are myeloid neoplasms characterized by disordered differentiation of hematopoietic stem cells and a predisposition to acute myeloid leukemia (AML). The underline pathogenesis remains unclear.
METHODS
METHODS
In this study, the trajectory of differentiation and mechanisms of leukemic transformation were explored through bioinformatics analysis of single-cell RNA-Seq data from hematopoietic stem and progenitor cells (HSPCs) in MDS patients.
RESULTS
RESULTS
Among the HSPC clusters, the proportion of common myeloid progenitor (CMP) was the main cell cluster in the patients with excess blasts (EB)/ secondary AML. Cell cycle analysis indicated the CMP of MDS patients were in an active proliferative state. The genes involved in the cell proliferation, such as MAML3 and PLCB1, were up-regulated in MDS CMP. Further validation analysis indicated that the expression levels of MAML3 and PLCB1 in patients with MDS-EB were significantly higher than those without EB. Patients with high expression of PLCB1 had a higher risk of transformation to AML. PLCB1 inhibitor can suppress proliferation, induce cell cycle arrest, and activate apoptosis of leukemic cells in vitro.
CONCLUSION
CONCLUSIONS
This study revealed the transcriptomic change of HSPCs in MDS patients along the pseudotime and indicated that PLCB1 plays a key role in the transformation of MDS into leukemia.
Identifiants
pubmed: 38632656
doi: 10.1186/s12967-024-05165-z
pii: 10.1186/s12967-024-05165-z
pmc: PMC11022353
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
359Subventions
Organisme : Wisdom Accumulation and Talent Cultivation Project of the Third Xiangya hospital of Central South University
ID : YX202212
Informations de copyright
© 2024. The Author(s).
Références
N Engl J Med. 2013 May 9;368(19):1781-90
pubmed: 23656643
Nat Commun. 2019 Jun 3;10(1):2395
pubmed: 31160568
N Engl J Med. 2020 Oct 1;383(14):1358-1374
pubmed: 32997910
Nat Med. 2022 Mar;28(3):557-567
pubmed: 35241842
Cell Death Discov. 2022 Mar 30;8(1):144
pubmed: 35354791
Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):3011-6
pubmed: 23388639
Front Immunol. 2019 Feb 08;10:173
pubmed: 30800127
Signal Transduct Target Ther. 2022 Oct 7;7(1):347
pubmed: 36202780
Exp Hematol Oncol. 2023 Jul 8;12(1):60
pubmed: 37422676
Cancer Cell Int. 2021 Aug 30;21(1):460
pubmed: 34461918
J Leukoc Biol. 2015 Nov;98(5):769-80
pubmed: 25977289
J Cell Biochem. 2016 Mar;117(3):566-73
pubmed: 26252946
Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):5009-14
pubmed: 21383193
Int J Hematol. 2020 Mar;111(3):352-359
pubmed: 31894534
J Transl Med. 2022 Nov 3;20(1):499
pubmed: 36329516
J Leukoc Biol. 2009 Sep;86(3):557-66
pubmed: 19451397
Nat Methods. 2017 Mar;14(3):309-315
pubmed: 28114287
Anticancer Res. 2018 Aug;38(8):4543-4547
pubmed: 30061220
Sci Transl Med. 2021 Sep 08;13(610):eabf0113
pubmed: 34516827
Cancer Res. 1998 Nov 15;58(22):5057-60
pubmed: 9823310
Cancer Med. 2021 Jun;10(12):3839-3847
pubmed: 34042280
Int J Mol Med. 2006 Aug;18(2):267-71
pubmed: 16820933
Genome Med. 2022 Sep 28;14(1):111
pubmed: 36171613
Am J Hematol. 2020 Nov;95(11):1399-1420
pubmed: 32744763
Leuk Res. 2012 Aug;36(8):974-81
pubmed: 22626984
J Biol Chem. 2000 Sep 29;275(39):30520-4
pubmed: 10913438
J Clin Oncol. 2011 Aug 20;29(24):3322-7
pubmed: 21788559