9h-purine-9-propanamine--6-amino-8-((6-iodo-1-3-benzodioxol-5-yl)thio)-n-(1-methylethyl)- and Precursor-Cell-Lymphoblastic-Leukemia-Lymphoma

The development of the dual Janus kinase 1/2 (JAK1/2) inhibitor ruxolitinib for the treatment of myeloproliferative neoplasms (MPNs) has led to studies of ruxolitinib in other clinical contexts, including JAK-mutated acute lymphoblastic leukemia (ALL). However, the limited ability of JAK inhibition to induce molecular or clinicopathological responses in MPNs suggests a need for development of better therapies for JAK kinase-dependent malignancies. Here, we demonstrate that heat shock protein 90 (HSP90) inhibition using a purine-scaffold HSP90 inhibitor in early clinical development is an effective therapeutic approach in JAK-dependent ALL and can overcome persistence to JAK-inhibitor therapy in ALL cells.

Topics: Animals; Benzodioxoles; Female; HSP90 Heat-Shock Proteins; Humans; Janus Kinase 1; Janus Kinase 2; Male; Mice; Mutation; Neoplasm Proteins; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Purines; Xenograft Model Antitumor Assays