Oncogenes and the Origins of Leukemias

Self-maintaining hematopoietic stem cells are a cell population that is primarily 'at risk' to malignant transformation, and the cell-of-origin for some leukemias. Tissue-specific stem cells replenish the different types of functional cells within a particular tissue to meet the demands of...

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Bibliographic Details
Published in:International journal of molecular sciences 2022-02, Vol.23 (4), p.2293
Main Author: Brown, Geoffrey
Format: Article
Language:English
Subjects:
Acute lymphoblastic leukemia
Artificial chromosomes
Blood
Blood platelets
Bone marrow
Cell differentiation
Cell lineage
Children
Cytokines
Gene expression
Genetic transformation
Genomics
Granulocytes
Hematopoietic stem cells
Immune system
Kinases
Leukemia
lineage fate
Lymphatic leukemia
Oncogenes
Population
Progenitor cells
Review
Stem cell transplantation
Stem cells
Transgenic mice
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Summary:Self-maintaining hematopoietic stem cells are a cell population that is primarily 'at risk' to malignant transformation, and the cell-of-origin for some leukemias. Tissue-specific stem cells replenish the different types of functional cells within a particular tissue to meet the demands of an organism. For hematopoietic stem cells, this flexibility is important to satisfy the changing requirements for a certain type of immune cell, when needed. From studies of the natural history of childhood acute lymphoblastic leukemia, an initial oncogenic and prenatal insult gives rise to a preleukemic clone. At least a second genomic insult is needed that gives rise to a leukemia stem cell: this cell generates a hierarchy of leukemia cells. For some leukemias, there is evidence to support the concept that one of the genomic insults leads to dysregulation of the tissue homeostatic role of hematopoietic stem cells so that the hierarchy of differentiating leukemia cells belongs to just one cell lineage. Restricting the expression of particular oncogenes in transgenic mice to hematopoietic stem and progenitor cells led to different human-like lineage-restricted leukemias. Lineage restriction is seen for human leukemias by virtue of their sub-grouping with regard to a phenotypic relationship to just one cell lineage.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23042293