Ruxolitinib Significantly Enhances in Vitro Apoptosis in Hodgkin Lymphoma and Primary Mediastinal B-Cell Lymphoma and Survival in a Lymphoma Xenograft Murine Model

Authors

Sanghoon Lee, New York Medical College
Tishi Shah, New York Medical College
Changhong Yin, New York Medical CollegeFollow
Jessica Hochberg, New York Medical CollegeFollow
Janet Ayello, New York Medical CollegeFollow
Carmella van de Ven, New York Medical CollegeFollow
Mitchell S. Cairo, New York Medical CollegeFollow

Journal Title

Oncotarget

First Page

9776

Last Page

9788

Document Type

Article

Publication Date

1-1-2018

Department

Pediatrics

Second Department

Pathology, Microbiology and Immunology

Third Department

Epidemiology and Community Health

Abstract

Hodgkin lymphoma (HL) and primary mediastinal B-cell lymphoma (PMBL) share similar molecular features by gene expression profiling. Frequent gains of chromosome 9p exhibit higher Janus Kinase 2 (JAK2) transcript levels with increased JAK2 activity, suggesting aberrant activity of JAK2 and STAT pathways. This signaling pathway alteration may in part play an important role in the pathogenesis and/or chemoradiotherapy resistance in HL and PMBL. Ruxolitinib is a potent and selective JAK1/JAK2 inhibitor, with activity against myeloproliferative neoplasms (MPNs) including those harboring the JAK2V617F mutation. We investigated the in vitro and in vivo efficacy of ruxolitinib and changes in downstream signaling pathways in HL and PMBL. We demonstrated that ruxolitinib significantly inhibited STAT signaling in both HL and PMBL with constitutively active JAK2 signaling. We also observed that ruxolitinib significantly induced in vitro anti-proliferative effects (p < 0.05) and increased programmed cell death (p < 0.05) against both HL and PMBL cells. Importantly, ruxolitinib significantly inhibited tumor progression by bioluminescence (p < 0.05) and significantly improved survival in HL (p = 0.0001) and PMBL (p < 0.0001) xenograft NSG mice. Taken altogether, these studies suggest that ruxolitinib may be a potential adjuvant targeted agent in the therapeutic approach in patients with high risk HL and PMBL.

Comments

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Recommended Citation

Lee, S., Shah, T., Yin, C., Hochberg, J., Ayello, J., van de Ven, C., & Cairo, M. (2018). Ruxolitinib Significantly Enhances in Vitro Apoptosis in Hodgkin Lymphoma and Primary Mediastinal B-Cell Lymphoma and Survival in a Lymphoma Xenograft Murine Model. Oncotarget, 9 (11), 9776-9788. https://doi.org/10.18632/oncotarget.24267

Publisher's Statement

Originally published in Oncotarget, 9(11), 9776-9788. The original material can be found here.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.