Uncovering the pathogenesis of large granular lymphocytic leukemia-novel STAT3 and STAT5b mutations.
Ann Med
; 46(3): 114-22, 2014 May.
Article
en En
| MEDLINE
| ID: mdl-24512550
ABSTRACT
Large granular lymphocytic (LGL) leukemia is an incurable chronic disease, characterized by clonal expansion of cytotoxic T- or NK-cells in blood and bone marrow. Cytopenias (anemia, neutropenia) and autoimmune disorders such as rheumatoid arthritis are the most common clinical manifestations of LGL leukemia. Recently, somatic activating STAT3 gene mutations were shown to be specific for LGL leukemia with a prevalence of up to 70%. Analogous mutations in the STAT5b gene were seen in a smaller proportion of patients. These gain-of-function mutations are located in the SH2 domain of STAT3 and affect the phosphotyrosine-SH2 interaction required for dimerization of STAT3. The mutations increase the phosphorylation of STAT3 and STAT5b and enhance the transcriptional activity of the mutated proteins. STAT3 and STAT5b mutations can be used as molecular markers for LGL leukemia diagnostics, and they present novel therapeutic targets for STAT3 and STAT5b inhibitors, which currently are in development for treatment of cancer and autoimmune disorders.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Factor de Transcripción STAT3
/
Factor de Transcripción STAT5
/
Leucemia Linfocítica Granular Grande
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Ann Med
Asunto de la revista:
MEDICINA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Finlandia