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Title: Adhesion-mediated self-renewal abilities of Ph+ blastoma cells

Abstract

The Philadelphia chromosome-positive blastoma, maintained by serial subcutaneous transplantation in nude mice, is a highly proliferating biological mass consisting of homogenous CD34{sup +}CD38{sup -} myeloblastoid cells. These cells newly evolved from pluripotent leukemia stem cells of chronic myeloid leukemia in the chronic phase. Therefore, this mass may provide a unique tool for better understanding cellular and molecular mechanisms of self-renewal of leukemia stem cells. In this paper, we demonstrated that intravenously injected blastoma cells can cause Ph+ blastic leukemia with multiple invasive foci in NOD/SCID mice but not in nude mice. In addition, using an in vitro culture system, we clearly showed that blastoma cell adhesion to OP9 stromal cells accelerates blastoma cell proliferation that is associated with up-regulation of BMI1 gene expression; increased levels of {beta}-catenin and the Notch1 intra-cellular domain; and changed the expression pattern of variant CD44 forms, which are constitutively expressed in these blastoma cells. These findings strongly suggest that adhesion of leukemic stem cells to stromal cells via CD44 might be indispensable for their cellular defense against attack by immune cells and for maintenance of their self-renewal ability.

Authors:
;  [1];  [2]; ;  [1];  [2];  [1]
  1. Department of Integrative Bioscience and Biomedical Engineering, Waseda University, 4-3-1 Ohkubo, Shinjuku-ku, Tokyo 169-555 (Japan)
  2. Institute of Medical Science, University of Tokyo, 4-6-1 Shirokenedai, Minato-ku, Tokyo (Japan)
Publication Date:
OSTI Identifier:
22202607
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 396; Journal Issue: 2; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL PROLIFERATION; GENE REGULATION; IN VITRO; MICE; MYELOID LEUKEMIA; PH VALUE; PHILADELPHIA CHROMOSOME; STEM CELLS

Citation Formats

Funayama, Keiji, Saito-Kurimoto, Yumi, Ebihara, Yasuhiro, Shimane, Miyuki, Nomura, Hitoshi, Tsuji, Ko-ichiro, and Asano, Shigetaka. Adhesion-mediated self-renewal abilities of Ph+ blastoma cells. United States: N. p., 2010. Web. doi:10.1016/J.BBRC.2010.03.172.
Funayama, Keiji, Saito-Kurimoto, Yumi, Ebihara, Yasuhiro, Shimane, Miyuki, Nomura, Hitoshi, Tsuji, Ko-ichiro, & Asano, Shigetaka. Adhesion-mediated self-renewal abilities of Ph+ blastoma cells. United States. https://doi.org/10.1016/J.BBRC.2010.03.172
Funayama, Keiji, Saito-Kurimoto, Yumi, Ebihara, Yasuhiro, Shimane, Miyuki, Nomura, Hitoshi, Tsuji, Ko-ichiro, and Asano, Shigetaka. 2010. "Adhesion-mediated self-renewal abilities of Ph+ blastoma cells". United States. https://doi.org/10.1016/J.BBRC.2010.03.172.
@article{osti_22202607,
title = {Adhesion-mediated self-renewal abilities of Ph+ blastoma cells},
author = {Funayama, Keiji and Saito-Kurimoto, Yumi and Ebihara, Yasuhiro and Shimane, Miyuki and Nomura, Hitoshi and Tsuji, Ko-ichiro and Asano, Shigetaka},
abstractNote = {The Philadelphia chromosome-positive blastoma, maintained by serial subcutaneous transplantation in nude mice, is a highly proliferating biological mass consisting of homogenous CD34{sup +}CD38{sup -} myeloblastoid cells. These cells newly evolved from pluripotent leukemia stem cells of chronic myeloid leukemia in the chronic phase. Therefore, this mass may provide a unique tool for better understanding cellular and molecular mechanisms of self-renewal of leukemia stem cells. In this paper, we demonstrated that intravenously injected blastoma cells can cause Ph+ blastic leukemia with multiple invasive foci in NOD/SCID mice but not in nude mice. In addition, using an in vitro culture system, we clearly showed that blastoma cell adhesion to OP9 stromal cells accelerates blastoma cell proliferation that is associated with up-regulation of BMI1 gene expression; increased levels of {beta}-catenin and the Notch1 intra-cellular domain; and changed the expression pattern of variant CD44 forms, which are constitutively expressed in these blastoma cells. These findings strongly suggest that adhesion of leukemic stem cells to stromal cells via CD44 might be indispensable for their cellular defense against attack by immune cells and for maintenance of their self-renewal ability.},
doi = {10.1016/J.BBRC.2010.03.172},
url = {https://www.osti.gov/biblio/22202607}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 396,
place = {United States},
year = {Fri May 28 00:00:00 EDT 2010},
month = {Fri May 28 00:00:00 EDT 2010}
}