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Leuk Lymphoma. 2015 May;56(5):1502-6. doi: 10.3109/10428194.2014.957204. Epub 2015 Jan 21.

Identification of mutant alleles of JAK3 in pediatric patients with acute lymphoblastic leukemia.

Author information

1
Department of Pediatrics, New York Medical College , Valhalla, NY , USA.

Abstract

Children with acute lymphoblastic leukemia (ALL) have an 80% chance of long-term survival. Despite the high rate of cure, children relapse, and recurrent ALL is difficult to cure with chemotherapeutic regimens. Therefore, improved biological understanding of ALL and the development of rationally designed therapeutics targeting molecules associated with the pathogenesis of ALL are essential. We identified missense and synonymous JAK3 mutations in 16 of 91 pediatric patients with ALL. The expression of JAK3(V722I) mutant caused the cytokine-independent activation of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling and conferred the factor-independent growth of murine interleukin-3 (IL-3)-dependent pro-B Ba/F3 cells. Importantly, inhibition of JAK3 by the known JAK3 inhibitor CP-690 550 converted the Ba/F3-JAK3(V722I) cells back to factor-dependent growth. These observations suggest that JAK3 may contribute to the pathogenesis of pediatric ALL and serve as an important therapeutic target which can be leveraged to improve outcomes for pediatric patients with ALL.

KEYWORDS:

Acute lymphoblastic leukemia; JAK3; mutant allele

PMID:
25146434
DOI:
10.3109/10428194.2014.957204
[Indexed for MEDLINE]

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