Close interaction with bone marrow mesenchymal stromal cells induces the development of cancer stem cell-like immunophenotype in B cell precursor acute lymphoblastic leukemia cells.

Abstract

Minimal residual disease of leukemia may reside in the bone marrow (BM) microenvironment and escape the effects of chemotherapeutic agents. This study investigated interactions between B cell precursor (BCP)-acute lymphoblastic leukemia (ALL) cells and BM mesenchymal stromal cells (BM-MSCs) in vitro. Five BCP-ALL cell lines established from pediatric patients and primary samples from a BCP-ALL patient were examined by flow cytometry and immunocytochemistry for expression of specific cell surface markers and cell adhesion proteins. The cell lines developed chemoresistance to commonly used anti-leukemic agents through adhesion to MSC-TERT cells in long-term culture. The change in chemosensitivity after adhering to BM-MSCs was associated with the expression of CD34, CD133, P-glycoprotein and BCRP/ABCG2, and downregulation of CD38. Similar phenotypic changes were observed in primary samples obtained by marrow aspiration or biopsy from a BCP-ALL patient. BM-MSC-adhering leukemia cells also showed deceleration of cell proliferation and expressed proteins in the Cadherin and Integrin pathways. These results suggest that BCP-ALL cells residing in the BM microenvironment may acquire chemoresistance by altering their phenotype to resemble that of cancer stem cells. Our results indicate that cell adhesion could be potentially targeted to improve the chemosensitivity of residual BCP-ALL cells in the BM microenvironment.

• Authors: Kentaro Kihira, Vipin Shankar Chelakkot, Hiroki Kainuma, Yosuke Okumura, Naoki Tsuboya, Satoshi Okamura, Kosuke Kurihara, Shotaro Iwamoto, Yoshihiro Komada, Hiroki Hori
• Journal: International journal of hematology (Int J Hematol) Vol. 112 Issue 6 Pg. 795-806 (Dec 2020) ISSN: 1865-3774 [Electronic] Japan
• PMID: 32862292 (Publication Type: Journal Article)

Chemical References

• Antigens, CD
• Antineoplastic Agents
• Cadherins

Topics

• Antigens, CD
• Antineoplastic Agents (pharmacology)
• Bone Marrow Cells (cytology)
• Cadherins (metabolism)
• Cell Adhesion (genetics)
• Cell Communication
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Child
• Humans
• Immunophenotyping
• Mesenchymal Stem Cells (physiology)
• Neoplasm, Residual
• Neoplastic Stem Cells (pathology, physiology)
• Precursor B-Cell Lymphoblastic Leukemia-Lymphoma (metabolism, pathology)
• Tumor Microenvironment