JAM-A As a Prognostic Factor and New Therapeutic Target in Multiple Myeloma

Overview

Journal Leukemia

Specialties Hematology
Oncology

Date 2017 Oct 25

PMID 29064484

Citations 40

Authors

A G Solimando

A Brandl

K Mattenheimer

C Graf

M Ritz

A Ruckdeschel

T Stuhmer

Z Mokhtari

M Rudelius

J Dotterweich

M Bittrich

V Desantis

R Ebert

P Trerotoli

M A Frassanito

A Rosenwald

A Vacca

H Einsele

F Jakob

A Beilhack

Affiliations

Soon will be listed here.

Abstract

Cell adhesion in the multiple myeloma (MM) microenvironment has been recognized as a major mechanism of MM cell survival and the development of drug resistance. Here we addressed the hypothesis that the protein junctional adhesion molecule-A (JAM-A) may represent a novel target and a clinical biomarker in MM. We evaluated JAM-A expression in MM cell lines and in 147 MM patient bone marrow aspirates and biopsies at different disease stages. Elevated JAM-A levels in patient-derived plasma cells were correlated with poor prognosis. Moreover, circulating soluble JAM-A (sJAM-A) levels were significantly increased in MM patients as compared with controls. Notably, in vitro JAM-A inhibition impaired MM migration, colony formation, chemotaxis, proliferation and viability. In vivo treatment with an anti-JAM-A monoclonal antibody (αJAM-A moAb) impaired tumor progression in a murine xenograft MM model. These results demonstrate that therapeutic targeting of JAM-A has the potential to prevent MM progression, and lead us to propose JAM-A as a biomarker in MM, and sJAM-A as a serum-based marker for clinical stratification.

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