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The Social Norm of Hematopoietic Stem Cells and Dysregulation in Leukemia

Journal

Publisher

MDPI
DOI: 10.3390/ijms23095063

Keywords

hematopoietic stem cells; leukemia; leukemia stem cells; lineage fate; oncogenes

Funding

  1. European Union [315902]

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The hematopoietic cell system is a complex ecosystem that can meet the needs of mature blood cells in both steady-state and emergency situations. It is highly integrated and social, adapting to different demands by generating cells biased towards specific lineages. Leukemia stem cells disrupt the cell hierarchy, being restricted to one lineage and able to alter the bone marrow stromal niches.
The hematopoietic cell system is a complex ecosystem that meets the steady-state and emergency needs of the production of the mature blood cell types. Steady-state hematopoiesis replaces worn out cells, and the hematopoietic system is highly adaptive to needs during, for example, an infection or bleeding. Hematopoiesis is highly integrated and the cell hierarchy behaves in a highly social manner. The social tailoring of hematopoietic stem cells to needs includes the generation of cells that are biased towards a cell lineage; these cells remain versatile and can still adopt a different pathway having made a lineage choice, and some cytokines instruct the lineage fate of hematopoietic stem and progenitor cells. Leukemia stem cells, which may well often arise from the transformation of a hematopoietic stem cell, sustain the hierarchy of cells for leukemia. Unlike hematopoietic stem cells, the offspring of leukemia stem cells belongs to just one cell lineage. The human leukemias are classified by virtue of their differentiating or partially differentiating cells belonging to just one cell lineage. Some oncogenes set the fate of leukemia stem cells to a single lineage. Therefore, lineage restriction may be largely an attribute whereby leukemia stem cells escape from the normal cellular society. Additional antisocial behaviors are that leukemia cells destroy and alter bone marrow stromal niches, and they can create their own niches.

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