LAROSE, H., N. PROKOPH, J.D. MATTHEWS, M. SCHLEDERER, S. HOGLER, A.F. ALSULAMI, S.P. DUCRAY, E. NUGLOZEH, M.F. FAZALUDEEN, A. ELMOUNA, M. CECCON, L. MOLOGNI, C. GAMBACORTI-PASSERINI, G. HOEFLER, Cosimo LOBELLO, Šárka POSPÍŠILOVÁ, A. JANIKOVA, W. WOESSMANN, C. DAMM-WELK, M. ZIMMERMANN, A. FEDOROVA, A. MALONE, O. SMITH, M. WASIK, G. INGHIRAMI, L. LAMANT, T.L. BLUNDELL, W. KLAPPER, O. MERKEL, G.A.A. BURKE, S. MIAN, I. ASHANKYTY, L. KENNER a Suzanne Dawn TURNER. Whole exome sequencing reveals NOTCH1 mutations in anaplastic large cell lymphoma and points to Notch both as a key pathway and a potential therapeutic target. haematologica. PAVIA: FERRATA STORTI FOUNDATION, 2021, roč. 106, č. 6, s. 1693-1704. ISSN 0390-6078. Dostupné z: https://dx.doi.org/10.3324/haematol.2019.238766. |
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@article{1782167, author = {Larose, H. and Prokoph, N. and Matthews, J.D. and Schlederer, M. and Hogler, S. and Alsulami, A.F. and Ducray, S.P. and Nuglozeh, E. and Fazaludeen, M.F. and Elmouna, A. and Ceccon, M. and Mologni, L. and GambacortiandPasserini, C. and Hoefler, G. and Lobello, Cosimo and Pospíšilová, Šárka and Janikova, A. and Woessmann, W. and DammandWelk, C. and Zimmermann, M. and Fedorova, A. and Malone, A. and Smith, O. and Wasik, M. and Inghirami, G. and Lamant, L. and Blundell, T.L. and Klapper, W. and Merkel, O. and Burke, G.A.A. and Mian, S. and Ashankyty, I. and Kenner, L. and Turner, Suzanne Dawn}, article_location = {PAVIA}, article_number = {6}, doi = {http://dx.doi.org/10.3324/haematol.2019.238766}, keywords = {SECRETASE INHIBITOR PF-03084014; ALK; TUMOR; EXPRESSION; NPM; GLYCOSYLATION; ADOLESCENTS; CRIZOTINIB; SIGNATURES; CHILDREN}, language = {eng}, issn = {0390-6078}, journal = {haematologica}, title = {Whole exome sequencing reveals NOTCH1 mutations in anaplastic large cell lymphoma and points to Notch both as a key pathway and a potential therapeutic target}, url = {https://haematologica.org/article/view/9725}, volume = {106}, year = {2021} }
TY - JOUR ID - 1782167 AU - Larose, H. - Prokoph, N. - Matthews, J.D. - Schlederer, M. - Hogler, S. - Alsulami, A.F. - Ducray, S.P. - Nuglozeh, E. - Fazaludeen, M.F. - Elmouna, A. - Ceccon, M. - Mologni, L. - Gambacorti-Passerini, C. - Hoefler, G. - Lobello, Cosimo - Pospíšilová, Šárka - Janikova, A. - Woessmann, W. - Damm-Welk, C. - Zimmermann, M. - Fedorova, A. - Malone, A. - Smith, O. - Wasik, M. - Inghirami, G. - Lamant, L. - Blundell, T.L. - Klapper, W. - Merkel, O. - Burke, G.A.A. - Mian, S. - Ashankyty, I. - Kenner, L. - Turner, Suzanne Dawn PY - 2021 TI - Whole exome sequencing reveals NOTCH1 mutations in anaplastic large cell lymphoma and points to Notch both as a key pathway and a potential therapeutic target JF - haematologica VL - 106 IS - 6 SP - 1693-1704 EP - 1693-1704 PB - FERRATA STORTI FOUNDATION SN - 03906078 KW - SECRETASE INHIBITOR PF-03084014 KW - ALK KW - TUMOR KW - EXPRESSION KW - NPM KW - GLYCOSYLATION KW - ADOLESCENTS KW - CRIZOTINIB KW - SIGNATURES KW - CHILDREN UR - https://haematologica.org/article/view/9725 N2 - Patients diagnosed with anaplastic large cell lymphoma (ALCL) are still treated with toxic multi-agent chemotherapy and as many as 25-50% of patients relapse. To understand disease pathology and to uncover novel targets for therapy, we performed whole-exome sequencing of anaplastic lymphoma kinase (ALK)(+) ALCL, as well as gene-set enrichment analysis. This revealed that the T-cell receptor and Notch pathways were the most enriched in mutations. In particular, variant T349P of NOTCH1, which confers a growth advantage to cells in which it is expressed, was detected in 12% of ALK(+) and ALK(-) ALCL patients' samples. Furthermore, we demonstrated that NPM-ALK promotes NOTCH1 expression through binding of STAT3 upstream of NOTCH1. Moreover, inhibition of NOTCH1 with gamma-secretase inhibitors or silencing by short hairpin RNA leads to apoptosis; co-treatment in vitro with the ALK inhibitor crizotinib led to additive/synergistic antitumor activity suggesting that this may be an appropriate combination therapy for future use in the circumvention of ALK inhibitor resistance. Indeed, crizotinib-resistant and -sensitive ALCL were equally sensitive to gamma-secretase inhibitors. In conclusion, we show a variant in the extracellular domain of NOTCH1 that provides a growth advantage to cells and confirm the suitability of the Notch pathway as a second-line druggable target in ALK(+) ALCL. ER -
LAROSE, H., N. PROKOPH, J.D. MATTHEWS, M. SCHLEDERER, S. HOGLER, A.F. ALSULAMI, S.P. DUCRAY, E. NUGLOZEH, M.F. FAZALUDEEN, A. ELMOUNA, M. CECCON, L. MOLOGNI, C. GAMBACORTI-PASSERINI, G. HOEFLER, Cosimo LOBELLO, Šárka POSPÍŠILOVÁ, A. JANIKOVA, W. WOESSMANN, C. DAMM-WELK, M. ZIMMERMANN, A. FEDOROVA, A. MALONE, O. SMITH, M. WASIK, G. INGHIRAMI, L. LAMANT, T.L. BLUNDELL, W. KLAPPER, O. MERKEL, G.A.A. BURKE, S. MIAN, I. ASHANKYTY, L. KENNER a Suzanne Dawn TURNER. Whole exome sequencing reveals NOTCH1 mutations in anaplastic large cell lymphoma and points to Notch both as a key pathway and a potential therapeutic target. \textit{haematologica}. PAVIA: FERRATA STORTI FOUNDATION, 2021, roč.~106, č.~6, s.~1693-1704. ISSN~0390-6078. Dostupné z: https://dx.doi.org/10.3324/haematol.2019.238766.
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