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Age related clonal hematopoiesis (ARCH)

Liran I. Shlush

Abstract

Age related alterations in the human blood system occur in B cells, T cells, cells of the innate system, as well as in hematopoietic stem and progenitor cells (HSPCs). Interestingly, age related, reduced genetic diversity can be identified both at the stem cell level, but also independently in B cells and T cells. This reduced diversity is most probably related to somatic mutations, or to changes in the micro-environmental niche. Either process can select for specific clones, or cause repeated evolutionary bottlenecks. This review will discuss the age related clonal expansions in the human HSPC pool, which was termed in the past Age Related Clonal Hematopoiesis (ARCH). ARCH is defined as the gradual, clonal expansion of HSPCs carrying specific, disruptive and recurrent genetic variants, in individuals without clear diagnosis of hematological malignancies. ARCH is not just associated with chronological aging but also with several other, age-related pathological conditions, including inflammation, vascular diseases, cancer mortality and high risk for hematological malignancies. While it remains unclear whether ARCH is a marker of aging or play an active role in these various pathophysiologies it is suggested here that treating or even preventing ARCH may prove to be beneficial for human health. This review also describes a decision tree for the diagnosis and follow-up for ARCH in a research setting.

  • Submitted July 20, 2017.
  • Accepted October 23, 2017.