Targeting the Epichaperome As an Effective Precision Medicine Approach in a Novel PML-SYK Fusion Acute Myeloid Leukemia

The epichaperome is a new cancer target defined, in part, by changes in the interaction strength between chaperone and co-chaperone proteins to form stable hyperconnected networks that support oncoprotein stability and are vital for tumor survival (Nature 2016, Nature Rev Cancer 2018 and Nature Med 2018). Cancers with this altered chaperone configuration may become susceptible to drugs that target the epichaperome, such as the inhibitor PU-H71. We have developed a novel flow cytometry-based test, the PU-FITC binding assay, to evaluate epichaperome levels at the single cell level and identify patients who are most likely to respond to PU-H71 treatment.A 61-year-old woman was diagnosed with an accelerated phase myeloproliferative neoplasm in 2013 after years of leukocytosis, arthritis, urticaria, and vasculitis. Cytogenetic analysis revealed t(9;15) involving the PML gene. Molecular studies were negative for BCR-ABL, PDGFRA/B and FGFR1 rearrangements as well as JAK2 mutation. Mutations in ETV6 and multiple ASXL1 subclones were present. She was treated with hydroxyurea and in Aug 2013 underwent matched unrelated donor allogeneic stem cell transplantation conditioned with Fludarabine/Melphalan, followed by 3 cycles of vidaza in 2014 for early recurrence. In Jan 2016, she relapsed and was treated with hydroxyurea. She also had painful ulcerations of toes, thought to be an atypical presentation of graft versus host disease complicated by her underlying Raynaud's disease and treated...
Source: Blood - Category: Hematology Authors: Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster I Source Type: research