Decreased IRF8 expression found in aging hematopoietic progenitor/stem cells

Leukemia. 2009 Feb;23(2):391-3. doi: 10.1038/leu.2008.176. Epub 2008 Jul 3.


To determine how aging impacts gene expression in hematopoietic stem cells (HSCs), human CD34+ cells from bone marrow (BMCD34+) and mobilized stem cell products (PBCD34+38-) were examined using microarray-based expression profiling. The age-associated expression changes in CD34+ cells were then compared to age-associated expression changes in murine HSCs. Interferon regulatory factor 8 (IRF8) was the only gene with age-associated expression changes in all analyses, decreasing its expression in human CD34+ cells and murine HSCs. Microarray-based expression profiling found that IRF8 expression also decreased with aging in human T-cells, suggesting that the effects of aging on IRF8 expression may extend to more differentiated populations of hematopoietic cells. Quantitative-RT/PCR studies confirmed that IRF8 mRNA expression decreased with aging in additional samples of BMCD34+, PBCD34+38-, and T-cells, and IRF8 protein expression was found to decrease with aging and to correlate with mRNA levels in PBCD34+ cells. The results suggest that IRF8 may be a novel biomarker of aging for hematopoietic cells. Given that inactivation of IRF8 causes CML-like syndromes in mice and decreased IRF8 expression occurs in human hematopoietic malignancies, it will be critical to determine if decreased IRF8 expression plays a role in the increased incidence of hematopoietic malignancies in older adults.

Publication types

  • Letter
  • Research Support, N.I.H., Extramural

MeSH terms

  • ADP-ribosyl Cyclase 1
  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aging*
  • Animals
  • Antigens, CD34
  • Hematopoietic Stem Cells / chemistry*
  • Humans
  • Interferon Regulatory Factors / analysis*
  • Interferon Regulatory Factors / genetics
  • Mice
  • Middle Aged
  • Young Adult


  • Antigens, CD34
  • Interferon Regulatory Factors
  • interferon regulatory factor-8
  • ADP-ribosyl Cyclase 1