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 Armstrong; Laura Leung; Stefan O. Ochiana; Gabriela Chiosis; Ross L. Levine; Maria Kleppe

doi:10.1182/blood-2015-03-635821

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^*

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

33 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 language	English (US)
Pages (from-to)	2479-2483
Number of pages	5
Journal	Blood
Volume	126
Issue number	22
DOIs	https://doi.org/10.1182/blood-2015-03-635821
State	Published - Nov 26 2015

Funding

ASJC Scopus subject areas

Hematology
Biochemistry
Cell Biology
Immunology

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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

@article{ea2e321fce2c43429075e70554c84a64,

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.",

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

note = "Publisher Copyright: {\textcopyright} 2015 by The American Society of Hematology.",

year = "2015",

month = nov,

day = "26",

doi = "10.1182/blood-2015-03-635821",

language = "English (US)",

volume = "126",

pages = "2479--2483",

journal = "Blood",

issn = "0006-4971",

publisher = "American Society of Hematology",

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Kucine, N, Marubayashi, S, Bhagwat, N, Papalexi, E, Koppikar, P, Martin, MS, Dong, L, Tallman, MS, Paietta, E, Wang, K, He, J, Lipson, D, Stephens, P, Miller, V, Rowe, JM, Teruya-Feldstein, J, Mullighan, CG, Ferrando, AA, Krivtsov, A, Armstrong, S, Leung, L, Ochiana, SO, Chiosis, G, Levine, RL & Kleppe, M 2015, 'Tumor-specific HSP90 inhibition as a therapeutic approach in JAK-mutant acute lymphoblastic leukemias', Blood, vol. 126, no. 22, pp. 2479-2483. https://doi.org/10.1182/blood-2015-03-635821

TY - JOUR

T1 - Tumor-specific HSP90 inhibition as a therapeutic approach in JAK-mutant acute lymphoblastic leukemias

AU - Kucine, Nicole

AU - Marubayashi, Sachie

AU - Bhagwat, Neha

AU - Papalexi, Efthymia

AU - Koppikar, Priya

AU - Martin, Marta Sanchez

AU - Dong, Lauren

AU - Tallman, Marty S.

AU - Paietta, Elisabeth

AU - Wang, Kai

AU - He, Jie

AU - Lipson, Doron

AU - Stephens, Phil

AU - Miller, Vince

AU - Rowe, Jacob M.

AU - Teruya-Feldstein, Julie

AU - Mullighan, Charles G.

AU - Ferrando, Adolfo A.

AU - Krivtsov, Andrei

AU - Armstrong, Scott

AU - Leung, Laura

AU - Ochiana, Stefan O.

AU - Chiosis, Gabriela

AU - Levine, Ross L.

AU - Kleppe, Maria

PY - 2015/11/26

Y1 - 2015/11/26

N2 - 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.

AB - 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.

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AN - SCOPUS:84948961990

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VL - 126

SP - 2479

EP - 2483

JO - Blood

JF - Blood

IS - 22

ER -

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

Abstract

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