Leukemia-Induced Cellular Senescence and Stemness Alterations in Mesenchymal Stem Cells Are Reversible upon Withdrawal of B-Cell Acute Lymphoblastic Leukemia Cells

Autor: Jean-Paul Vernot, Natalia-Del Pilar Vanegas, Paola Fernanda Ruiz-Aparicio, Gloria Inés Uribe, Adriana Linares-Ballesteros
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
senescence
QH301-705.5
mesenchymal stem cells (MSC)
Cell
Article
Catalysis
Inorganic Chemistry
B-cell acute lymphoblastic leukemia (B-ALL)
03 medical and health sciences
0302 clinical medicine
Tumor Microenvironment
medicine
Humans
Biology (General)
Physical and Theoretical Chemistry
leukemic niche (LN)
QD1-999
Molecular Biology
Cells
Cultured
Cellular Senescence
Spectroscopy
Cell Proliferation
bone marrow microenvironment
Chemistry
Cell growth
Organic Chemistry
Mesenchymal stem cell
Cell Differentiation
Mesenchymal Stem Cells
General Medicine
reversible senescence
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Cell cycle
Hematopoietic Stem Cells
medicine.disease
Computer Science Applications
Haematopoiesis
Leukemia
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Cancer research
Bone marrow
Stem cell
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 15
International Journal of Molecular Sciences, Vol 22, Iss 8166, p 8166 (2021)
ISSN: 1422-0067
DOI: 10.3390/ijms22158166
Popis: Leukemic cell growth in the bone marrow (BM) induces a very stressful condition. Mesenchymal stem cells (MSC), a key component of this BM niche, are affected in several ways with unfavorable consequences on hematopoietic stem cells favoring leukemic cells. These alterations in MSC during B-cell acute lymphoblastic leukemia (B-ALL) have not been fully studied. In this work, we have compared the modifications that occur in an in vitro leukemic niche (LN) with those observed in MSC isolated from B-ALL patients. MSC in this LN niche showed features of a senescence process, i.e., altered morphology, increased senescence-associated β-Galactosidase (SA-βGAL) activity, and upregulation of p53 and p21 (without p16 expression), cell-cycle arrest, reduced clonogenicity, and some moderated changes in stemness properties. Importantly, almost all of these features were found in MSC isolated from B-ALL patients. These alterations rendered B-ALL cells susceptible to the chemotherapeutic agent dexamethasone. The senescent process seems to be transient since when leukemic cells are removed, normal MSC morphology is re-established, SA-βGAL expression is diminished, and MSC are capable of re-entering cell cycle. In addition, few cells showed low γH2AX phosphorylation that was reduced to basal levels upon cultivation. The reversibility of the senescent process in MSC must impinge important biological and clinical significance depending on cell interactions in the bone marrow at different stages of disease progression in B-ALL.
Databáze: OpenAIRE
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