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World J Hematol. Feb 6, 2013; 2(1): 1-5
Published online Feb 6, 2013. doi: 10.5315/wjh.v2.i1.1
Bone marrow cell death and proliferation: Controlling mechanisms in normal and leukemic state
Morito Kurata, Shiho Suzuki, Shinya Abe, Iichiroh Onishi, Masanobu Kitagawa
Morito Kurata, Shiho Suzuki, Shinya Abe, Iichiroh Onishi, Masanobu Kitagawa, Department of Comprehensive Pathology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519, Japan
Author contributions: Suzuki S, Abe S and Onishi I offered suggestions regarding the conduct of the manuscript; Kurata M and Kitagawa M wrote the manuscript.
Correspondence to: Masanobu Kitagawa, MD, PhD, Professor, Chair, Department of Comprehensive Pathology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. masa.pth2@tmd.ac.jp
Telephone: +81-3-58035173 Fax: +81-3-58030123
Received: June 22, 2012
Revised: November 30, 2012
Accepted: January 5, 2013
Published online: February 6, 2013
Abstract

Bone marrow cell death and proliferation are regulated by multiple factors including genetic and epigenetic alterations of hematopoietic cells, crosstalk of hematopoietic cells with bone marrow mesenchymal cells through direct cell-cell interaction or cytokine/chemokine production, vascularity of the bone marrow, and interactions of sympathetic nerve system with hematopoiesis. Cell proliferation usually predominates over cell death in neoplastic processes such as leukemia and myeloproliferative neoplasms, while apoptotic processes also have a significant role in the pathogenesis of myelodysplastic syndromes. Recently, hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs) have been identified and their characters on self renewal process, differentiation, cell dynamics and drug resistance have been implicated. Although most leukemia cells are initially sensitive to chemo- or radiotherapy, LSCs are resistant and considered to be the basis for disease relapse after initial response. HSCs and LSCs may use similar interactions with bone marrow microenvironment. However, bone marrow microenvironment called niche should influence the normal as well as malignant hematopoiesis in different manners. Recent studies have expanded the number of cell types constituting bone marrow niche and made the issue more complex. Since the majority of excellent and contributing studies on bone marrow niches have been performed in animal models, niches in human tissues are beginning to be localized and characterized. In this article, we summarize the relation of hematopoietic cells with niches and hope to point a hint to the novel strategy for treatment of malignant proliferation of hematopoietic cells.

Keywords: Bone marrow; Hematopoietic stem cells; Niche; Apoptosis; Leukemia