Close interaction with bone marrow mesenchymal stromal cells induces the development of cancer stem cell-like immunophen
- PDF / 4,591,471 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 85 Downloads / 223 Views
ORIGINAL ARTICLE
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 Kentaro Kihira1 · Vipin Shankar Chelakkot1 · Hiroki Kainuma2 · Yosuke Okumura1 · Naoki Tsuboya1 · Satoshi Okamura1,2 · Kosuke Kurihara1,2 · Shotaro Iwamoto1 · Yoshihiro Komada1 · Hiroki Hori1,2 Received: 10 April 2020 / Revised: 5 August 2020 / Accepted: 25 August 2020 © Japanese Society of Hematology 2020
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. Keywords B cell precursor acute lymphoblastic leukemia · Bone marrow mesenchymal stromal cell · Cancer stem cell · Leukemic stem cell · Cellular interaction
Introduction Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells, characterized by the generation of a large number of immature lymphocytes in the bone marrow (BM). Advanced treatment strategies developed over Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12185-020-02981-z) contains supplementary material, which is available to authorized users. * Hiroki Hori [email protected]‑u.ac.jp 1
Department of Pediatrics, Mie University Graduate School of Medicine, Tsu, Japan
Department of Medical Education, Mie University Graduate School of Medicine, 2‑174, Edobashi, Tsu, Mie 514‑8507, Japan
2
the last several decades have increased the survival rate in childhood ALL from under 10% in the 1960 s to about 90% in 2015 [1]. Despite this progress in treatment, the survival rate for relapsed ALL remains poor [2]. Minimal residual disease (MRD) after treatment is a w
Data Loading...
