Preclinical and clinical efficacy of XPO1/CRM1 inhibition by the karyopherin inhibitor KPT-330 in Ph+ leukemias-Reference-Cited by-同舟云学术

Preclinical and clinical efficacy of XPO1/CRM1 inhibition by the karyopherin inhibitor KPT-330 in Ph+ leukemias

Published:2013-10-24 Issue:17 Volume:122 Page:3034-3044
ISSN:0006-4971
Container-title:Blood
language:en
Short-container-title:

Author:

Walker Christopher J.¹,Oaks Joshua J.¹,Santhanam Ramasamy¹²,Neviani Paolo¹³,Harb Jason G.¹,Ferenchak Gregory¹,Ellis Justin J.¹,Landesman Yosef⁴,Eisfeld Ann-Kathrin¹,Gabrail Nash Y.⁵,Smith Carrie L.⁵,Caligiuri Michael A.²³,Hokland Peter⁶,Roy Denis Claude⁷,Reid Alistair⁸,Milojkovic Dragana⁸,Goldman John M.⁸,Apperley Jane⁸,Garzon Ramiro²³,Marcucci Guido²³,Shacham Sharon⁴,Kauffman Michael G.⁴,Perrotti Danilo¹³⁸

Affiliation:

1. Human Cancer Genetics Program, Department Molecular Virology Immunology and Medical Genetics,

2. Department of Internal Medicine, and

3. Comprehensive Cancer Center, The Ohio State University, Columbus, OH;

4. Karyopharm Therapeutics Incorporated, Natick MA;

5. Gabrail Cancer Center, Canton, OH;

6. Department of Hematology, Aarhus University Hospital, Aarhus, Denmark;

7. Department of Hematology-Oncology, Maisonneuve-Rosemont Hospital and University of Montreal, Montreal, QC, Canada; and

8. Department of Haematology, Hammersmith Hospital, Imperial College London, London, United Kingdom

Abstract

Key Points XPO1/CRM1 is upregulated in a BCR-ABL1 kinase-dependent and -independent manner and negatively controls PP2A tumor suppressor activity. KPT-330 antagonizes survival of TKI-resistant Ph+ acute leukemias in vitro, in CML-BC animals, and in a CML-AP patient.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Link

http://ashpublications.org/blood/article-pdf/122/17/3034/1370471/3034.pdf

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