The success of tyrosine kinase inhibitors (TKIs) in treating chronic myeloid leukemia (CML) depends on the requirement for BCR-ABL1 kinase activity in CML progenitors. However, CML quiescent HSCs are TKI resistant and represent a BCR-ABL1 kinase–independent disease reservoir. Here we have shown that persistence of leukemic HSCs in BM requires inhibition of the tumor suppressor protein phosphatase 2A (PP2A) and expression — but not activity — of the
Paolo Neviani, Jason G. Harb, Joshua J. Oaks, Ramasamy Santhanam, Christopher J. Walker, Justin J. Ellis, Gregory Ferenchak, Adrienne M. Dorrance, Carolyn A. Paisie, Anna M. Eiring, Yihui Ma, Hsiaoyin C. Mao, Bin Zhang, Mark Wunderlich, Philippa C. May, Chaode Sun, Sahar A. Saddoughi, Jacek Bielawski, William Blum, Rebecca B. Klisovic, Janelle A. Solt, John C. Byrd, Stefano Volinia, Jorge Cortes, Claudia S. Huettner, Steffen Koschmieder, Tessa L. Holyoake, Steven Devine, Michael A. Caligiuri, Carlo M. Croce, Ramiro Garzon, Besim Ogretmen, Ralph B. Arlinghaus, Ching-Shih Chen, Robert Bittman, Peter Hokland, Denis-Claude Roy, Dragana Milojkovic, Jane Apperley, John M. Goldman, Alistair Reid, James C. Mulloy, Ravi Bhatia, Guido Marcucci, Danilo Perrotti
PP2A activity is inhibited in CML HSCs.