Hematopoietic Transfer of the Anti-Cancer and Lifespan-Extending Capabilities of A Genetically Engineered Blood System

Abstract

A causal relationship exists among the aging process, organ decay and dis-function, and the occurrence of various diseases including cancer. A genetically engineered mouse model, termed Eklf K74R/K74R or Eklf(K74R), carrying mutation on the well-conserved sumoylation site of the hematopoietic transcription factor KLF1/ EKLF has been generated that possesses extended lifespan and healthy characteristics including cancer resistance. We show that the high anti-cancer capability of the Eklf(K74R) mice are gender-, age-and genetic background-independent. Significantly, the anti-cancer capability and extended lifespan characteristics of Eklf(K74R) mice could be transferred to wild-type mice via transplantation of their bone marrow mononuclear cells. Targeted/global gene expression profiling analysis has identified changes of the expression of specific proteins and cellular pathways in the leukocytes of the Eklf(K74R) that are in the directions of anti-cancer and/or anti-aging. This study demonstrates the feasibility of developing a novel hematopoietic/ blood system for long-term anti-cancer and, potentially, for anti-aging.