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


Authors: 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.; Armstrong, S.; Leung, L.; Ochiana, S. O.; Chiosis, G.; Levine, R. L.; Kleppe, M.
Article Title: Tumor-specific HSP90 inhibition as a therapeutic approach in JAK-mutant acute lymphoblastic leukemias
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. © 2015 by The American Society of Hematology.
Keywords: controlled study; unclassified drug; nonhuman; animal cell; mouse; animal experiment; animal model; acute lymphoblastic leukemia; janus kinase; leukemia cell; heat shock protein 90 inhibitor; heat shock protein 90; single drug dose; leukocyte count; mutant; spleen cell; spleen size; pu h 71; human; priority journal; article
Journal Title: Blood
Volume: 126
Issue: 22
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2015-11-26
Start Page: 2479
End Page: 2483
Language: English
DOI: 10.1182/blood-2015-03-635821
PROVIDER: scopus
PMCID: PMC4661170
PUBMED: 26443624
DOI/URL:
Notes: Article -- Export Date: 7 January 2016 -- 2479 -- Source: Scopus
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MSK Authors
  1. Martin Stuart Tallman
    408 Tallman
  2. Nicole Kucine
    4 Kucine
  3. Ross Levine
    469 Levine
  4. Gabriela Chiosis
    216 Chiosis
  5. Neha Bhagwat
    21 Bhagwat
  6. Maria Kleppe
    28 Kleppe
  7. Scott Allen Armstrong
    108 Armstrong
  8. Laura K Leung
    4 Leung
  9. Stefan Ovidiu Ochiana
    11 Ochiana
  10. Lauren   Dong
    4 Dong