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 M. 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 & 5 others Laura Leung, Stefan O. Ochiana, Gabriela Chiosis, Ross L. Levine, Maria Kleppe

Research output: Contribution to journalArticle

14 Citations (Scopus)

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

Fingerprint

HSP90 Heat-Shock Proteins
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Specific heat
Tumors
Janus Kinase 1
Janus Kinases
Scaffolds
Janus Kinase 2
Neoplasms
Therapeutics
INCB018424
purine

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Kucine, N., Marubayashi, S., Bhagwat, N., Papalexi, E., Koppikar, P., Martin, M. S., ... 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

Tumor-specific HSP90 inhibition as a therapeutic approach in JAK-mutant acute lymphoblastic leukemias. / Kucine, Nicole; Marubayashi, Sachie; Bhagwat, Neha; Papalexi, Efthymia; Koppikar, Priya; Martin, Marta Sanchez; Dong, Lauren; Tallman, Marty S.; Paietta, Elisabeth M.; Wang, Kai; He, Jie; Lipson, Doron; Stephens, Phil; Miller, Vince; Rowe, Jacob M.; Teruya-Feldstein, Julie; Mullighan, Charles G.; Ferrando, Adolfo A.; Krivtsov, Andrei; Armstrong, Scott; Leung, Laura; Ochiana, Stefan O.; Chiosis, Gabriela; Levine, Ross L.; Kleppe, Maria.

In: Blood, Vol. 126, No. 22, 26.11.2015, p. 2479-2483.

Research output: Contribution to journalArticle

Kucine, N, Marubayashi, S, Bhagwat, N, Papalexi, E, Koppikar, P, Martin, MS, Dong, L, Tallman, MS, Paietta, EM, 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
Kucine N, Marubayashi S, Bhagwat N, Papalexi E, Koppikar P, Martin MS et al. Tumor-specific HSP90 inhibition as a therapeutic approach in JAK-mutant acute lymphoblastic leukemias. Blood. 2015 Nov 26;126(22):2479-2483. https://doi.org/10.1182/blood-2015-03-635821
Kucine, Nicole ; Marubayashi, Sachie ; Bhagwat, Neha ; Papalexi, Efthymia ; Koppikar, Priya ; Martin, Marta Sanchez ; Dong, Lauren ; Tallman, Marty S. ; Paietta, Elisabeth M. ; Wang, Kai ; He, Jie ; Lipson, Doron ; Stephens, Phil ; Miller, Vince ; Rowe, Jacob M. ; Teruya-Feldstein, Julie ; Mullighan, Charles G. ; Ferrando, Adolfo A. ; Krivtsov, Andrei ; Armstrong, Scott ; Leung, Laura ; Ochiana, Stefan O. ; Chiosis, Gabriela ; Levine, Ross L. ; Kleppe, Maria. / Tumor-specific HSP90 inhibition as a therapeutic approach in JAK-mutant acute lymphoblastic leukemias. In: Blood. 2015 ; Vol. 126, No. 22. pp. 2479-2483.
@article{a3b4b394c61649ae9ad322384312ea90,
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 Paietta, {Elisabeth M.} 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",
year = "2015",
month = "11",
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",
number = "22",

}

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 M.

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.

UR - http://www.scopus.com/inward/record.url?scp=84948961990&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84948961990&partnerID=8YFLogxK

U2 - 10.1182/blood-2015-03-635821

DO - 10.1182/blood-2015-03-635821

M3 - Article

VL - 126

SP - 2479

EP - 2483

JO - Blood

JF - Blood

SN - 0006-4971

IS - 22

ER -