Lessons to cancer from studies of leukemia and hematopoiesis

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Abstract

The starting point to describing the origin and nature of any cancer must be knowledge about how the normal counterpart tissue develops. New principles to the nature of hematopoietic stem cells have arisen in recent years. In particular, hematopoietic stem cells can “choose” a cell lineage directly from a spectrum of the end-cell options, and are, therefore, a heterogeneous population of lineage affiliated/biased cells. These cells remain versatile because the developmental trajectories of hematopoietic stem and progenitor cells are broad. From studies of human acute myeloid leukemia, leukemia is also a hierarchy of maturing or partially maturing cells that are sustained by leukemia stem cells at the apex. This cellular hierarchy model has been extended to a wide variety of human solid tumors, by the identification of cancer stem cells, and is termed the cancer stem cell model. At least, two genomic insults are needed for cancer, as seen from studies of human childhood acute lymphoblastic leukemia. There are signature mutations for some leukemia’s and some relate to a transcription factor that guides the cell lineage of developing hematopoietic stem/progenitor cells. Similarly, some oncogenes restrict the fate of leukemia stem cells and their offspring to a single maturation pathway. In this case, a loss of intrinsic stem cell versatility seems to be a property of leukemia stem cells. To provide more effective cures for leukemia, there is the need to find ways to eliminate leukemia stem cells.
Original languageEnglish
Article number993915
Number of pages13
JournalFrontiers in cell and developmental biology
Volume10
Early online date20 Sept 2022
DOIs
Publication statusE-pub ahead of print - 20 Sept 2022

Bibliographical note

Funding Information:
This project received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement No. 315902. GB was the lead within the Marie Curie Initial Training Network DECIDE (Decision-making within cells and differentiation entity therapies).

Publisher Copyright:
Copyright © 2022 Brown.

Keywords

  • leukemia
  • leukemia stem cells
  • cancer stem cells
  • oncogenes
  • therapies

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