Paradoxical down-regulation of p16 mRNA with advancing age in acute myeloid leukemia.
Aging is generally considered to be the consequence of stem cell attrition caused by the activity of tumor suppressor pathways that censor potentially malignant clones by eliciting apoptosis or senescence. An important effector of aging is the cyclindependent kinase inhibitor p16(INK4a), which is also a known suppressor of cancer. The expression of p16(INK4a) is very low or absent in young organisms but increases with advancing age. We recently showed that, unlike healthy cells, acute myeloid leukemia (AML) derived blasts show a down-regulation of p16(INK4a) mRNA with increasing age. Based on this observation we hypothesize that suppression of defense mechanisms which protect older cells against cellular and DNA damage might facilitate oncogenesis in older individuals.
de Jonge
Hendrik J M
HJ
Division of Pediatric Oncology/Hematology, Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Woolthuis
Carolien M
CM
de Bont
Eveline S J M
ES
Huls
Gerwin
G
D000375:Aging / Q000235:genetics* / Q000473:pathology / Q000502:physiology; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000502:physiology; D004249:DNA Damage / Q000235:genetics / Q000502:physiology; D015536:Down-Regulation / Q000235:genetics* / Q000502:physiology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D007962:Leukocytes / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology
D019941:Cyclin-Dependent Kinase Inhibitor p16; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins