We developed an HSP90 inhibitor (aminoxyrone) which is active as a pan-leukemia inhibitor against LSCs without the induction of any HSR and a dual proteasome-HDAC6 hybrid inhibitor (RTS-V), with sensitivity in BCR-ABL1+ TKI resistant BCP-ALL....Aminoxyrone is effective in preclinical TKI (2nd and 3rd generation) resistant cell line models in vitro and in vivo, induces apoptosis in primary BCR-ABL1+ BCP-ALL and in Ph-like BCP-ALL patient-derived LSCs, without inducing any HSR.