Tumor-specific HSP90 inhibition as a therapeutic approach in JAK-mutant acute lymphoblastic leukemias

Nicole Kucine, Sachie Marubayashi, Neha Bhagwat, Efthymia Papalexi, Priya Koppikar, Marta Sanchez Martin, Lauren Dong, Marty S. Tallman, Elisabeth Paietta, Kai Wang, Jie He, Doron Lipson, Phil Stephens, Vince Miller, Jacob M. Rowe, Julie Teruya-Feldstein, Charles G. Mullighan, Adolfo A. Ferrando, Andrei Krivtsov, Scott ArmstrongLaura Leung, Stefan O. Ochiana, Gabriela Chiosis, Ross L. Levine, Maria Kleppe

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The development of the dual Janus kinase 1/2 (JAK1/2) inhibitor ruxolitinib for the treatment of myeloproliferativeneoplasms (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.

Original languageEnglish (US)
Pages (from-to)2479-2483
Number of pages5
JournalBlood
Volume126
Issue number22
DOIs
StatePublished - Nov 26 2015

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Kucine, N., Marubayashi, S., Bhagwat, N., Papalexi, E., Koppikar, P., Martin, M. S., Dong, L., Tallman, M. S., Paietta, E., Wang, K., He, J., Lipson, D., Stephens, P., Miller, V., Rowe, J. M., Teruya-Feldstein, J., Mullighan, C. G., Ferrando, A. A., Krivtsov, A., ... Kleppe, M. (2015). Tumor-specific HSP90 inhibition as a therapeutic approach in JAK-mutant acute lymphoblastic leukemias. Blood, 126(22), 2479-2483. https://doi.org/10.1182/blood-2015-03-635821