Truncating Erythropoietin Receptor Rearrangements in Acute Lymphoblastic Leukemia.
Cancer Cell
; 29(2): 186-200, 2016 Feb 08.
Article
em En
| MEDLINE
| ID: mdl-26859458
ABSTRACT
Chromosomal rearrangements are a hallmark of acute lymphoblastic leukemia (ALL) and are important ALL initiating events. We describe four different rearrangements of the erythropoietin receptor gene EPOR in Philadelphia chromosome-like (Ph-like) ALL. All of these rearrangements result in truncation of the cytoplasmic tail of EPOR at residues similar to those mutated in primary familial congenital polycythemia, with preservation of the proximal tyrosine essential for receptor activation and loss of distal regulatory residues. This resulted in deregulated EPOR expression, hypersensitivity to erythropoietin stimulation, and heightened JAK-STAT activation. Expression of truncated EPOR in mouse B cell progenitors induced ALL in vivo. Human leukemic cells with EPOR rearrangements were sensitive to JAK-STAT inhibition, suggesting a therapeutic option in high-risk ALL.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores da Eritropoetina
/
Ordem dos Genes
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
Limite:
Humans
Idioma:
En
Revista:
Cancer Cell
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos