Putative mechanism of action of HDAC inhibitors in MF. HSP90 is known to associate with HDAC6. JAK2 proteins (both wild-type and mutant proteins) are known clients of HSP90, which stabilizes these proteins. The use of a HDAC inhibitor leads to inhibition of HDAC6, with subsequent acetylation of HSP90 and resultant targeting of JAK2 proteins for proteosomal degradation. This mechanism may contribute at least in part to the down-modulation of the JAK2V617F protein observed with the use of HDAC inhibitors.