Enhancing mitochondrial function in vivo rescues MDS-like anemia induced by pRb deficiency
Taha Sen, Mayur Jain, Magnus Gram, Alexander Mattebo, Shamit Soneji, Carl R Walkley, Sofie Singbrant
EXPERIMENTAL HEMATOLOGY | ELSEVIER SCIENCE INC | Published : 2020
Erythropoiesis is intimately coupled to cell division, and deletion of the cell cycle regulator retinoblastoma protein (pRb) causes anemia in mice. Erythroid-specific deletion of pRb has been found to result in inefficient erythropoiesis because of deregulated coordination of cell cycle exit and mitochondrial biogenesis. However, the pathophysiology remains to be fully described, and further characterization of the link between cell cycle regulation and mitochondrial function is needed. To this end we further assessed conditional erythroid-specific deletion of pRb. This resulted in macrocytic anemia, despite elevated levels of erythropoietin (Epo), and an accumulation of erythroid progenitor..View full abstract
LWe thank Dr. Johan Flygare for intellectual input, Dr. Eva Hellstrom-Lindberg for expert advice regarding MDS-related anemia, Dr. David Thorburn for valuable discussions regarding the use of bezafibrate, Dr. Abdul G. Alattar for kindly assisting in experimental work, and the Lund Stem Cell Center FACS Core for expert assistance with cell sorting. This research was supported by the Swedish Cancer Society (fellowship to SoSi), the Swedish Society for Medical Research (fellowship to SoSi), the Crafoordska Foundation, the Ake Wiberg Foundation, the Clas Groschinsky's Memory Foundation, the Gunnar Nilsson Cancer Foundation, the Royal Physiographic Society of Lund, and the Harald & Greta Jeansson Foundation.