Activating alleles of JAK3 in acute megakaryoblastic leukemia.
Cancer Cell
; 10(1): 65-75, 2006 Jul.
Article
en En
| MEDLINE
| ID: mdl-16843266
ABSTRACT
Tyrosine kinases are aberrantly activated in numerous malignancies, including acute myeloid leukemia (AML). To identify tyrosine kinases activated in AML, we developed a screening strategy that rapidly identifies tyrosine-phosphorylated proteins using mass spectrometry. This allowed the identification of an activating mutation (A572V) in the JAK3 pseudokinase domain in the acute megakaryoblastic leukemia (AMKL) cell line CMK. Subsequent analysis identified two additional JAK3 alleles, V722I and P132T, in AMKL patients. JAK3(A572V), JAK3(V722I), and JAK3(P132T) each transform Ba/F3 cells to factor-independent growth, and JAK3(A572V) confers features of megakaryoblastic leukemia in a murine model. These findings illustrate the biological importance of gain-of-function JAK3 mutations in leukemogenesis and demonstrate the utility of proteomic approaches to identifying clinically relevant mutations.
Buscar en Google
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Tirosina Quinasas
/
Leucemia Experimental
/
Leucemia Megacarioblástica Aguda
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Cancer Cell
Asunto de la revista:
NEOPLASIAS
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos