Caner Saygin, Pu Zhang, Jacob Stauber, Ibrahim Aldoss, Adam S Sperling, Lachelle D Weeks, Marlise R Luskin, Todd C Knepper, Pankhuri Wanjari, Peng Wang, Angela M Lager, Carrie Fitzpatrick, Jeremy P Segal, Mehdi Gharghabi, Sandeep Gurbuxani, Girish Venkataraman, Jason X Cheng, Bart J Eisfelder, Oliver Bohorquez, Anand A Patel, Sheethal Umesh Nagalakshmi, Savita Jayaram, Olatoyosi M Odenike, Richard A Larson, Lucy A Godley, Daniel A Arber, Christopher J Gibson, Nikhil C Munshi, Guido Marcucci, Benjamin L Ebert, John M Greally, Ulrich Steidl, Rosa Lapalombella, Bijal D Shah, Wendy Stock
Myeloid neoplasms arise from pre-existing clonal hematopoiesis (CH), however the role of CH in pathogenesis of ALL is unknown. We found that 18% of adult ALL cases harbored TP53, and 16% had myeloid CH-associated gene mutations. ALL with myeloid mutations (MyM) had distinct genetic and clinical characteristics, associated with inferior survival. By using single cell proteogenomic analysis, we demonstrated that myeloid mutations were present years before the diagnosis of ALL, and a subset of these clones expanded over time to manifest as dominant clones in ALL...
December 27, 2023: Blood cancer discovery