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Reduced Osteogenic Differentiation Potential In Vivo in Acute Myeloid Leukaemia Patients Correlates with Decreased BMP4 Expression in Mesenchymal Stromal Cells

  • Pedro L. Azevedo (Stem Cell Laboratory, Bone Marrow Transplantation Unit, National Cancer Institute (INCA)) ;
  • Rhayra B. Dias (Research Division, National Institute of Traumatology and Orthopedics) ;
  • Liebert P. Nogueira (Oral Research Laboratory, Department of Biomaterials, Institute of Clinical Dentistry, University of Oslo) ;
  • Simone Maradei (Bone Marrow Transplantation Unit, National Cancer Institute (INCA)) ;
  • Ricardo Bigni (Hematology Service, National Cancer Institute (INCA)) ;
  • Jordana S. R. Aragao (Hematology Service, National Cancer Institute (INCA)) ;
  • Eliana Abdelhay (Stem Cell Laboratory, Bone Marrow Transplantation Unit, National Cancer Institute (INCA)) ;
  • Renata Binato (Stem Cell Laboratory, Bone Marrow Transplantation Unit, National Cancer Institute (INCA))
  • Received : 2021.08.05
  • Accepted : 2021.10.07
  • Published : 2022.05.30

Abstract

The osteogenic differentiation potential of mesenchymal stromal cells (hMSCs) is an essential process for the haematopoiesis and the maintenance of haematopoietic stem cells (HSCs). Therefore, the aim of this work was to evaluate this potential in hMSCs from AML patients (hMSCs-AML) and whether it is associated with BMP4 expression. The results showed that bone formation potential in vivo was reduced in hMSCs-AML compared to hMSCs from healthy donors (hMSCs-HD). Moreover, the fact that hMSCs-AML were not able to develop supportive haematopoietic cells or to differentiate into osteocytes suggests possible changes in the bone marrow microenvironment. Furthermore, the expression of BMP4 was decreased, indicating a lack of gene expression committed to the osteogenic lineage. Overall, these alterations could be associated with changes in the maintenance of HSCs, the leukaemic transformation process and the development of AML.

Keywords

Acknowledgement

This work was financially supported by FAPERJ (E-26/202.874/2015) and CNPq (308121/2018-0).

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