Critical role of the NOTCH ligand JAG2 in self-renewal of myeloma cells

Blood Cells, Molecules & Diseases
David ChironCatherine Pellat-Deceunynck

Abstract

The purpose of this study was to identify the pathways associated with the ability of CD138(+) human myeloma cells to form colonies in a serum-free semi-solid human collagen-based assay. Only 26% (7 of 27) of human myeloma cell lines were able to spontaneously form colonies. This spontaneous clonogenic growth correlated with the expression of the NOTCH ligand JAG2 (p<0.001). Blocking JAG-NOTCH interactions with NOTCH-Fc chimeric molecules impaired self-colony formation, indicating a role for JAG-NOTCH pathway in colony formation. In two cell lines, silencing of JAG2 blocked both colony formation and in vivo tumor formation in immunocompromised mice. RT-PCR and flow cytometry analysis revealed that JAG2 is often expressed by CD138(+) primary cells. Our results indicate that spontaneous clonogenic growth of myeloma cells requires the expression of JAG2.

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Citations

Aug 8, 2014·BioMed Research International·Sanjay de MelWee-Joo Chng
Dec 10, 2013·Journal of Hematology & Oncology·Joshua KellnerZihai Li
Feb 21, 2013·Expert Opinion on Therapeutic Targets·Sojoong ChoiEok-Soo Oh
Jul 10, 2014·Blood·Benoît TessoulinCatherine Pellat-Deceunynck
Jan 8, 2015·Critical Reviews in Oncology/hematology·Rajendra Gharbaran
Aug 27, 2015·Oncotarget·Michela ColomboRaffaella Chiaramonte
Mar 29, 2019·JBMR Plus·Emily G Atkinson, Jesús Delgado-Calle

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