J 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

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
Název: CEITEC 2020 (Akronym: CEITEC2020)
Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020
675712, interní kód MU
Název: ALK Activation as a target of TRAanslational Science (ALKATRAS): Break free from cancer (Akronym: ALKATRAS)
Investor: Evropská unie, ALK Activation as a target of TRAanslational Science (ALKATRAS): Break free from cancer, MSCA Marie Skłodowska-Curie Actions (Excellent Science)