open access

Vol 52, No 4 (2021)
Review article
Published online: 2021-08-31
Submitted: 2021-07-07
Accepted: 2021-07-14
Get Citation

Leukemic stem cells: clone wars

Wiesław Wiktor Jędrzejczak1
DOI: 10.5603/AHP.2021.0052
·
Acta Haematol Pol 2021;52(4):268-271.
Affiliations
  1. Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, Poland

open access

Vol 52, No 4 (2021)
REVIEW ARTICLE
Published online: 2021-08-31
Submitted: 2021-07-07
Accepted: 2021-07-14

Abstract

Leukemic stem cells arise as the effect of mutations of normal hematopoietic cells and overgrow normal hematopoietic tissue. They may also infiltrate other organs. While they begin their life from mutations, they continue to mutate, creating daughter leukemic stem cells that harbor two, three, or more mutations, and these mutations can be different in different daughter stem cells of the same parental line in the same individual. These daughter stem cells then compete between themselves as to which one will overgrow the host tissues with its progeny, and finally will contribute to the host’s death. This process can be shaped by therapy, which may preferentially eliminate some subclones and simultaneously favor others. To eliminate such stem cells, therapy is needed that will preferentially attack their self-renewal.

Abstract

Leukemic stem cells arise as the effect of mutations of normal hematopoietic cells and overgrow normal hematopoietic tissue. They may also infiltrate other organs. While they begin their life from mutations, they continue to mutate, creating daughter leukemic stem cells that harbor two, three, or more mutations, and these mutations can be different in different daughter stem cells of the same parental line in the same individual. These daughter stem cells then compete between themselves as to which one will overgrow the host tissues with its progeny, and finally will contribute to the host’s death. This process can be shaped by therapy, which may preferentially eliminate some subclones and simultaneously favor others. To eliminate such stem cells, therapy is needed that will preferentially attack their self-renewal.

Get Citation

Keywords

stem cells, self-renewal, oncogenic mutations

About this article
Title

Leukemic stem cells: clone wars

Journal

Acta Haematologica Polonica

Issue

Vol 52, No 4 (2021)

Article type

Review article

Pages

268-271

Published online

2021-08-31

DOI

10.5603/AHP.2021.0052

Bibliographic record

Acta Haematol Pol 2021;52(4):268-271.

Keywords

stem cells
self-renewal
oncogenic mutations

Authors

Wiesław Wiktor Jędrzejczak

References (20)
  1. Nowell P, Hungerford D. A minute chromosome in chronic granulocytic leukemia. Science. 1960; 132(3438): 1488.
  2. Ren R. Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia. Nat Rev Cancer. 2005; 5(3): 172–183.
  3. Abelson HT, Rabstein LS. Influence of prednisolone on Moloney leukemogenic virus in BALB-c mice. Cancer Res. 1970; 30(8): 2208–2212.
  4. Gross L. The search for viruses as etiological agents in leukemia and malignant lymphomas: the role of the happy accident and the prepared mind. Cancer Res. 1980; 40(9): 3405–3407.
  5. Knudson AG. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A. 1971; 68(4): 820–823.
  6. Gilliland DG. Hematologic malignancies. Curr Opin Hematol. 2001; 8(4): 189–191.
  7. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016; 127(20): 2391–2405.
  8. Steensma DP. Clinical consequences of clonal hematopoiesis of indeterminate potential. Blood Adv. 2018; 2(22): 3404–3410.
  9. Kishtagari A, Jha BK, Maciejewski JP. TET2 mutations and clonal dynamics. Oncotarget. 2019; 10(21): 2010–2011.
  10. Milholland B, Suh Y, Vijg J. Mutation and catastrophe in the aging genome. Exp Gerontol. 2017; 94: 34–40.
  11. Nadeau JH. Modifier genes in mice and humans. Nat Rev Genet. 2001; 2(3): 165–174.
  12. Wong TN, Miller CA, Klco JM, et al. Rapid expansion of preexisting nonleukemic hematopoietic clones frequently follows induction therapy for de novo AML. Blood. 2016; 127(7): 893–897.
  13. Petti AA, Williams SR, Miller CA, et al. A general approach for detecting expressed mutations in AML cells using single cell RNA-sequencing. Nat Commun. 2019; 10(1): 3660.
  14. Ding Li, Ley TJ, Larson DE, et al. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature. 2012; 481(7382): 506–510.
  15. Miles LA, Bowman RL, Merlinsky TR, et al. Single-cell mutation analysis of clonal evolution in myeloid malignancies. Nature. 2020; 587(7834): 477–482.
  16. Horne GA, Copland M. Approaches for targeting self-renewal pathways in cancer stem cells: implications for hematological treatments. Expert Opin Drug Discov. 2017; 12(5): 465–474.
  17. Yang L, Shi P, Zhao G, et al. Targeting cancer stem cell pathways for cancer therapy. Signal Transduct Target Ther. 2020; 5(1): 8.
  18. Cortes JE, Gutzmer R, Kieran MW, et al. Hedgehog signaling inhibitors in solid and hematological cancers. Cancer Treat Rev. 2019; 76: 41–50.
  19. Cortes JE, Heidel FH, Hellmann A, et al. Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Leukemia. 2019; 33(2): 379–389.
  20. Kim J, Aftab BT, Tang JY, et al. Itraconazole and arsenic trioxide inhibit Hedgehog pathway activation and tumor growth associated with acquired resistance to smoothened antagonists. Cancer Cell. 2013; 23(1): 23–34.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk, Poland
tel.:+48 58 320 94 94, fax:+48 58 320 94 60, e-mail: journals@viamedica.pl