Umeshkumar Vekariya, Monika Maria Toma, Margaret Nieborowska-Skorska, Bac Viet Le, Marie-Christine Caron, Anna-Mariya Kukuyan, Katherine Sullivan-Reed, Paulina Podszywalow-Bartnicka, Kumaraswamy Naidu Chitrala, Jessica Atkins, Malgorzata Drzewiecka, Wanjuan Feng, Joe Chan, Srinivas Chatla, Konstantin Golovine, Jaroslav Jelinek, Tomasz Sliwinski, Jayashri Ghosh, Ksenia Matlawska-Wasowska, Gurushankar Chandramouly, Reza Nejati, Mariusz A Wasik, Stephen Sykes, Katarzyna Piwocka, Emir Hadzijusufovic, Peter Valent, Richard T Pomerantz, George Morton, Wayne Childers, Huaqing Zhao, Elisabeth Paietta, Ross L Levine, Martin S Tallman, Hugo Fernandez, Mark R Litzow, Gaorav Gupta, Jean-Yves Masson, Tomasz Skorski
Leukemia cells accumulate DNA damage but altered DNA repair mechanisms protect them from apoptosis. We showed here that formaldehyde generated by serine/one-carbon cycle metabolism contributed to accumulation of toxic DNA-protein crosslinks (DPCs) in leukemia cells, especially in driver clones harboring oncogenic tyrosine kinases [OTKs: FLT3(ITD), JAK2(V617F), BCR/ABL1]. To counteract this effect, OTKs enhanced the expression of DNA polymerase theta (POLq) by ERK1/2 serine/threonine kinase-dependent inhibition of c-CBL E3 ligase-mediated ubiquitination of POLq and its proteasomal degradation...
December 29, 2022: Blood