Fig. 5. Restoration of trilineage hematopoiesis following treatment with bortezomib and vorinostat containing chemotherapy regimen in a refractory patient.

A Bone marrow aspirates of case 3b (see Table 2) at the time of relapse post-transplant and post-treatment with bortezomib and vorinostat-containing chemotherapy regimen are shown at ×10 and ×100 magnification. Flow-based MRD and RT-PCR for the KMT2A-MLLT1 oncogene present in this patient were both negative post-treatment. B Model of proteasome and HDAC inhibition in KMT2Ar leukemia. Proteasome inhibitors deplete H2Bub1 leading to downregulation of the KMT2A gene expression program and accumulation of the KMT2A fusion which triggers caspase 8¹². HDACi prevent aggresome formation and increase in histone acetylation and death gene induction promoting apoptosis.