Fiche publication
Date publication
mars 2021
Journal
Blood cancer journal
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GARRIDO Carmen
,
Dr PAIS DE BARROS Jean-Paul
,
Dr QUERE Ronan
,
Pr GIRODON François
,
Dr BELLAYE Pierre-Simon
Tous les auteurs :
Mshaik R, Simonet J, Georgievski A, Jamal L, Bechoua S, Ballerini P, Bellaye PS, Mlamla Z, Pais de Barros JP, Geissler A, Francin PJ, Girodon F, Garrido C, Quéré R
Lien Pubmed
Résumé
T-cell and B-cell acute lymphoblastic leukemias (T-ALL, B-ALL) are aggressive hematological malignancies characterized by an accumulation of immature T- or B-cells. Although patient outcomes have improved, novel targeted therapies are needed to reduce the intensity of chemotherapy and improve the prognosis of high-risk patients. Using cell lines, primary cells and patient-derived xenograft (PDX) models, we demonstrate that ALL cells viability is sensitive to NVP-BEP800, an ATP-competitive inhibitor of Heat shock protein 90 (HSP90). Furthermore, we reveal that lymphocyte-specific SRC family kinases (SFK) are important clients of the HSP90 chaperone in ALL. When PDX mice are treated with NVP-BEP800, we found that there is a decrease in ALL progression. Together, these results demonstrate that the chaperoning of SFK by HSP90 is involved in the growth of ALL. These novel findings provide an alternative approach to target SRC kinases and could be used for the development of new treatment strategies for ALL.
Référence
Blood Cancer J. 2021 Mar 18;11(3):61
