BCR-ABL1–induced inactivation of PP2A. BCR-ABL1 mediates the post-transcriptional up-regulation of SET, a phosphoprotein that functions as an inhibitor of the serine/threonine phosphatase PP2A. This activity is mediated via the heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1). The activation of PP2A recruits the SH2 domain–containing protein tyrosine phosphatase 1 (SHP1), which dephosphorylates BCR-ABL1, resulting in BCR-ABL1 down-regulation through proteosomal degradation. Pharmacologic activation of PP2A with forskolin or fingolimod (FTY720) results in abrogation of CML cell proliferation, including cells expressing the pan-resistant mutation T315I.