title: Potential relationship between inadequate response to DNA damage and development of myelodysplastic syndrome.
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.
authors.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.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhou
authors.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. ChenP3@uthscsa.edu.
authors.forename: Peishuai
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Hematology, Northern Jiangsu People's Hospital, Yangzhou 225001, China. gujianyz@sina.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Gu
authors.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. bishopa@uthscsa.edu.
authors.forename: Alexander J R
authors.initials: AJ
authors.lastname: Bishop
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, 37 Kent Street, Woolloongabba, QLD 4102, Australia. l.scott3@uq.edu.au.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Scott
authors.affiliation: The Cancer Therapy Research Center, UTHSCSA, 7979 Wurzbach Road, San Antonio, TX 78229, USA. hastye@uthscsa.edu.
authors.forename: Paul
authors.initials: P
authors.lastname: Hasty
authors.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. rebel@uthscsa.edu.
authors.forename: Vivienne I
authors.initials: VI
authors.lastname: Rebel
mesh_terms: D000375:Aging; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D044127:Epigenesis, Genetic; D042822:Genomic Instability; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human