2020
IL10RA modulates crizotinib sensitivity in NPM1-ALK(+) anaplastic large cell lymphoma
PROKOPH, N.; N.A. PROBST; L.C. LEE; J.M. MONAHAN; J.D. MATTHEWS et al.Základní údaje
Originální název
IL10RA modulates crizotinib sensitivity in NPM1-ALK(+) anaplastic large cell lymphoma
Autoři
PROKOPH, N.; N.A. PROBST; L.C. LEE; J.M. MONAHAN; J.D. MATTHEWS; H.C. LIANG; K. BAHNSEN; I.A. MONTES-MOJARRO; E. KARACA-ATABAY; G.G. SHARMA; V. MALIK; H. LAROSE; S.D. FORDE; S.P. DUCRAY; Cosimo LOBELLO; Q. WANG; S.L. LUAN; Šárka POSPÍŠILOVÁ; C. GAMBACORTI-PASSERINI; G.A.A. BURKE; S. PERVEZ; A. ATTARBASCHI; A. JANIKOVA; H. PACQUEMENT; J. LANDMAN-PARKER; A. LAMBILLIOTTE; G. SCHLEIERMACHER; W. KLAPPER; R. JAUCH; W. WOESSMANN; G. VASSAL; L. KENNER; O. MERKEL; L. MOLOGNI; R. CHIARLE; L. BRUGIERES; B. GEOERGER; I. BARBIERI a Suzanne Dawn TURNER
Vydání
Blood, Washington DC, USA, American Society of Hematology, 2020, 0006-4971
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
30205 Hematology
Stát vydavatele
Spojené státy
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Impakt faktor
Impact factor: 23.629
Označené pro přenos do RIV
Ano
Kód RIV
RIV/00216224:14740/20:00118318
Organizační jednotka
Středoevropský technologický institut
UT WoS
EID Scopus
Klíčová slova anglicky
NON-HODGKIN-LYMPHOMA; MOLECULAR SIGNATURES; PEDIATRIC-PATIENTS; TYROSINE KINASE; SOLID TUMORS; ALK; EXPRESSION; CHILDREN; ADOLESCENTS; GENE
Štítky
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 11. 3. 2021 18:23, Mgr. Pavla Foltynová, Ph.D.
Anotace
V originále
Anaplastic large cell lymphoma (ALCL) is a T-cell malignancy predominantly driven by a hyperactive anaplastic lymphoma kinase (ALK) fusion protein. ALK inhibitors, such as crizotinib, provide alternatives to standard chemotherapy with reduced toxicity and side effects. Children with lymphomas driven by nucleophosmin 1 (NPM1)-ALK fusion proteins achieved an objective response rate to ALK inhibition therapy of 54% to 90% in clinical trials; however, a subset of patients progressed within the first 3 months of treatment. The mechanism for the development of ALK inhibitor resistance is unknown. Through genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) activation and knockout screens in ALCL cell lines, combined with RNA sequencing data derived from ALK inhibitor-relapsed patient tumors, we show that resistance to ALK inhibition by crizotinib in ALCL can be driven by aberrant upregulation of interleukin 10 receptor subunit alpha (IL10RA). Elevated IL10RA expression rewires the STAT3 signaling pathway, bypassing otherwise critical phosphorylation by NPM1-ALK. IL-10RA expression does not correlate with response to standard chemotherapy in pediatric patients, suggesting that a combination of crizotinib and chemotherapy could prevent ALK inhibitor resistance-specific relapse.
Návaznosti
| LQ1601, projekt VaV |
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| 675712, interní kód MU |
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