![Model of mismatch repair (MMR)–dependent age-related changes in the hematopoietic stem cell pool. At birth few, if any, genetic alterations occur in the hematopoietic stem cell (HSC) pool (blue ovals). Over the next 45 years, HSCs accumulate low levels of DNA damage (ie, base-mispairs and/or microsatellite instability [MSI]; red caret) that either escape MMR or are caused by MLH1 loss. After 45 years of age, accumulation of damage accelerates (2 red carets) due to subsequent loss of MLH1 and MMR capacity potentially leading to HSC loss of function (dashed ovals) and/or HSC malignant transformation (green ovals).](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/120/16/10.1182_blood-2012-07-441220/4/zh89991295490001.jpeg?Expires=1722763081&Signature=VT0FmWtHWk6UWX8Tx3e0OQXrZb-PnAobYCsZF2flft0sMbpPNMmrkyYJaCVPA~NO1q-6NcEuvAA-xr8yQz~-iBEnkSrVjiw8WT~utXRJMMulia7uxyP6-qY3wj1M-nUvimnI5iNu2Q-UEuFr9vTnj6Ni7b595~3N0lKrWrZJC0ctSC-DUHGFb9PyKDM7qEU2A30h0rF~Zt1IR1qBcbNJKAq4H14Znb~1AWpzIoUcWWqQqMdVo9yzl~CXYYyJf7wwQKyz-gILuo3hcwzZOjj7Js8REk-Tkp4Yw~Qs~Lg-WiDKuKgTWvy5MC2heQIQZrcIq5SY0EH40Ih1WgLBHk46Ig__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
Model of mismatch repair (MMR)–dependent age-related changes in the hematopoietic stem cell pool. At birth few, if any, genetic alterations occur in the hematopoietic stem cell (HSC) pool (blue ovals). Over the next 45 years, HSCs accumulate low levels of DNA damage (ie, base-mispairs and/or microsatellite instability [MSI]; red caret) that either escape MMR or are caused by MLH1 loss. After 45 years of age, accumulation of damage accelerates (2 red carets) due to subsequent loss of MLH1 and MMR capacity potentially leading to HSC loss of function (dashed ovals) and/or HSC malignant transformation (green ovals).
