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Potential relationship between inadequate response to DNA damage and development of myelodysplastic syndrome.

Zhou T, Chen P, Gu J, Bishop AJ, Scott LM, Hasty P, Rebel VI - Int J Mol Sci (2015)

Bottom Line: Nevertheless, normal HSC aging is associated with a noticeable decline in regenerative potential and possible changes in other functions.Myelodysplastic syndrome (MDS) is an age-associated hematopoietic malignancy, characterized by abnormal blood cell maturation and a high propensity for leukemic transformation.It is furthermore thought to originate in a HSC and to be associated with the accrual of multiple genetic and epigenetic aberrations.

View Article: PubMed Central - PubMed

Affiliation: Greehey Children's Cancer Research Center, University of Texas Health Science Center San Antonio (UTHSCSA), 8403 Floyd Curl Drive, San Antonio, TX 78229, USA. zhoubaipi@gmail.com.

ABSTRACT
Hematopoietic stem cells (HSCs) are responsible for the continuous regeneration of all types of blood cells, including themselves. To ensure the functional and genomic integrity of blood tissue, a network of regulatory pathways tightly controls the proliferative status of HSCs. Nevertheless, normal HSC aging is associated with a noticeable decline in regenerative potential and possible changes in other functions. Myelodysplastic syndrome (MDS) is an age-associated hematopoietic malignancy, characterized by abnormal blood cell maturation and a high propensity for leukemic transformation. It is furthermore thought to originate in a HSC and to be associated with the accrual of multiple genetic and epigenetic aberrations. This raises the question whether MDS is, in part, related to an inability to adequately cope with DNA damage. Here we discuss the various components of the cellular response to DNA damage. For each component, we evaluate related studies that may shed light on a potential relationship between MDS development and aberrant DNA damage response/repair.

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Related in: MedlinePlus

Cellular response to DNA damage. Depicted are the major cellular processes (in black letters) that are initiated after DNA damage. In red are the genes indicated that are related to these processes and that have been found mutated in MDS patients. The underlined symbols indicate genes that are perturbed in hereditary syndromes associated with a high risk of developing MDS (see also Table 1). MDS-associated perturbations in TP53 can be both inherited (Li-Fraumeni syndrome) as well as acquired.
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ijms-16-00966-f002: Cellular response to DNA damage. Depicted are the major cellular processes (in black letters) that are initiated after DNA damage. In red are the genes indicated that are related to these processes and that have been found mutated in MDS patients. The underlined symbols indicate genes that are perturbed in hereditary syndromes associated with a high risk of developing MDS (see also Table 1). MDS-associated perturbations in TP53 can be both inherited (Li-Fraumeni syndrome) as well as acquired.

Mentions: To protect against permanent DNA damage and its potentially deleterious effects, cells are armed with a plethora of defense mechanisms, including DNA damage sensing mechanisms, cell cycle arrest, apoptosis, senescence and differentiation and DNA repair (Figure 2). Which of these are used depends on the nature and the amount of damage, the cell type and stage of the cell cycle in which the damage occurred [67,68]. Failure to properly execute these processes, may lead to the propagation of cells containing genomic abnormalities. Below follows a more detailed description of the various processes utilized by cells in response to DNA damage. Evidence for a possible link to MDS in humans will be discussed.


Potential relationship between inadequate response to DNA damage and development of myelodysplastic syndrome.

Zhou T, Chen P, Gu J, Bishop AJ, Scott LM, Hasty P, Rebel VI - Int J Mol Sci (2015)

Cellular response to DNA damage. Depicted are the major cellular processes (in black letters) that are initiated after DNA damage. In red are the genes indicated that are related to these processes and that have been found mutated in MDS patients. The underlined symbols indicate genes that are perturbed in hereditary syndromes associated with a high risk of developing MDS (see also Table 1). MDS-associated perturbations in TP53 can be both inherited (Li-Fraumeni syndrome) as well as acquired.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307285&req=5

ijms-16-00966-f002: Cellular response to DNA damage. Depicted are the major cellular processes (in black letters) that are initiated after DNA damage. In red are the genes indicated that are related to these processes and that have been found mutated in MDS patients. The underlined symbols indicate genes that are perturbed in hereditary syndromes associated with a high risk of developing MDS (see also Table 1). MDS-associated perturbations in TP53 can be both inherited (Li-Fraumeni syndrome) as well as acquired.
Mentions: To protect against permanent DNA damage and its potentially deleterious effects, cells are armed with a plethora of defense mechanisms, including DNA damage sensing mechanisms, cell cycle arrest, apoptosis, senescence and differentiation and DNA repair (Figure 2). Which of these are used depends on the nature and the amount of damage, the cell type and stage of the cell cycle in which the damage occurred [67,68]. Failure to properly execute these processes, may lead to the propagation of cells containing genomic abnormalities. Below follows a more detailed description of the various processes utilized by cells in response to DNA damage. Evidence for a possible link to MDS in humans will be discussed.

Bottom Line: Nevertheless, normal HSC aging is associated with a noticeable decline in regenerative potential and possible changes in other functions.Myelodysplastic syndrome (MDS) is an age-associated hematopoietic malignancy, characterized by abnormal blood cell maturation and a high propensity for leukemic transformation.It is furthermore thought to originate in a HSC and to be associated with the accrual of multiple genetic and epigenetic aberrations.

View Article: PubMed Central - PubMed

Affiliation: Greehey Children's Cancer Research Center, University of Texas Health Science Center San Antonio (UTHSCSA), 8403 Floyd Curl Drive, San Antonio, TX 78229, USA. zhoubaipi@gmail.com.

ABSTRACT
Hematopoietic stem cells (HSCs) are responsible for the continuous regeneration of all types of blood cells, including themselves. To ensure the functional and genomic integrity of blood tissue, a network of regulatory pathways tightly controls the proliferative status of HSCs. Nevertheless, normal HSC aging is associated with a noticeable decline in regenerative potential and possible changes in other functions. Myelodysplastic syndrome (MDS) is an age-associated hematopoietic malignancy, characterized by abnormal blood cell maturation and a high propensity for leukemic transformation. It is furthermore thought to originate in a HSC and to be associated with the accrual of multiple genetic and epigenetic aberrations. This raises the question whether MDS is, in part, related to an inability to adequately cope with DNA damage. Here we discuss the various components of the cellular response to DNA damage. For each component, we evaluate related studies that may shed light on a potential relationship between MDS development and aberrant DNA damage response/repair.

Show MeSH
Related in: MedlinePlus