Bone marrow mesenchymal stem cells are functionally remodeled after complete remission of acute myeloid leukemia

Acute myeloid leukemia (AML) is a type of hematological malignancy, induces the normal bone marrow (BM) microenvironment to supporting AML cells. Although previous work revealed that functional remodeling of BM endothelial progenitor cells after complete remission (CR), as another important component of the BM microenvironment, whether AML-induced BM mesenchymal stem cells (MSCs) can also be functional modified after CR is largely unknown.

Patients with de novo AML, patients with AML who achieved complete remission (AML-CR) and healthy controls (HC) were enrolled. Flow cytometry was used to exploring the regulatory effects of BM MSCs on cluster of differentiation CD34⁺ cells or CD3⁺ cells. Immunocytochemistry and senescence-associated β-galactosidase (SA-β-gal) staining was used to detect the number of senescent BM MSCs. Ribonucleic acid sequencing (RNA-seq) analysis and quantitative real-time reverse transcription PCR (qRT-PCR) were used to detect the transcription profile and characteristics of BM MSCs. An AML-CR mouse model was used to verify the remodeling of BM MSCs after CR.

Dysfunctional BM MSCs in AML patients were subsequently recovered in AML-CR patients, including their differentiation potential, apoptosis ratio, expression of cytokines and regulatory roles, which were return to near HC MSCs. Moreover, the transcriptomic profile of CR MSCs was also remodeled and transformed to be more similar to that of HC MSCs. Our data further revealed that the expression of senescent-related genes, the number of senescent cells in AML-CR patients were reduced, and that CR MSCs regained the ability to be reinduced to senescence by AML cells.

Our findings describe the functional remodeling of BM MSCs among patients with AML, AML-CR patients and HC, and the reduction in the number of senescent BM MSCs associated with BM MSC remodeling. Our work provides a new perspective indicating that AML-modified BM MSCs can be remodeled to support normal hematopoietic stem cells (HSCs) in AML-CR patients, which may contribute to promoting normal hematopoiesis recovery for AML patients.