Authors
Christian Pecquet, Thomas Balligand, Ilyas Chachoua, Anita Roy, Gaelle Vertenoeil, Didier Colau, Emanuel Fertig, Caroline Marty, Harini Nivarthi, Jean-Philippe Defour, Erica Xu, Eva Hug, Heinz Gisslinger, Bettina Gisslinger, Martin Schalling, Ilaria Carola Casetti, Elisa Rumi, Daniela Pietra, Chiara Cavalloni, Luca Arcaini, Mario Cazzola, Norio Komatsu, Yoshihiko Kihara, Yoshitaka Sunami, Yoko Edahiro, Marito Araki, Isabelle Plo, William Vainchenker, Robert Kralovics, Stefan N Constantinescu
Publication date
2018/11/29
Journal
Blood
Volume
132
Issue
Supplement 1
Pages
4-4
Publisher
American Society of Hematology
Description
Background
Mutant calreticulins carrying the sequence translated after a+ 1 frameshift at the C-terminus are major drivers of myeloproliferative neoplasms (MPNs). These mutant CALRs bind and activate TpoR/MPL in cells co-expressing TpoR and mutant CALRs, resulting in persistent JAK2-STAT5 signaling. Whether mutant CALR proteins are secreted, thus acting in trans on other cells, is not known.
Aims
Our objectives were to: 1) assess the direct TpoR-mutant CALR interaction both when expressed in the same or in different cells; 2) determine whether mutant CALRs are secreted; and 3) determine whether mutant CALR can act as extracellular cytokines.
Methods
Engineered CALR and TpoR mutants were analyzed by a combination of biochemical approaches (bioluminescence resonance energy transfer, recombinant protein production), functional assays (cell growth and transcriptional assays, flow cytometry …
Scholar articles
C Pecquet, T Balligand, I Chachoua, A Roy… - Blood, 2018