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 |
