Vol 5, No 1 (2014)
Review paper
Published online: 2014-05-23

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Resistance mechanisms of hematopoietic and leukemic stem cells

Agnieszka Ciomber, Iwona Mitrus
Hematologia 2014;5(1):30-39.

Abstract

Hematopoietic stem cells (HSC) are a special type of somatic stem cells. They are characterized by the ability to divide an unlimited number of times and to differentiate into all types of blood cells. The pool of HSC must therefore be sufficient for the whole life of an organism. All genetic alterations of a stem cell will be retained by its daughter cells and they may lead to disturbances of hematopoiesis. There are several mechanisms that protect somatic HSC. Part of HSC remain inquiescent state, the G0 phase of the cell cycle, which reduces the risk of mutations. These cells are also characterized by increased expression of proteins associated with apoptosis resistance, DNA repair and toxin removal. Other surface proteins provide protection against attack by specific and/or nonspecific immune system cells. Also, HSC are protected by bone marrow microenvironment. Similar mechanisms affect the resistance of the so-called leukemic stem cells (LSC). Resistance of these cells is also influenced by mutations that occur during carcinogenesis. Presence of cancerstem cells (CSC) is considered to be a major cause of treatment failure: chemo-and radiotherapy both reduce the number of leukemic cells in the body, but CSC which remain after treatment may cause recurrence of the disease. Understanding resistance mechanisms of HSC might exert a significant impact on further developments in medicine. Foremostly, such knowledge would permit understanding the background and fine details of some hematologic disorders as well as developing novel therapeutic strategies.



Hematology in Clinical Practice