| Literature DB >> 19838194 |
Charles G Mullighan, J Racquel Collins-Underwood, Letha A A Phillips, Michael G Loudin, Wei Liu, Jinghui Zhang, Jing Ma, Elaine Coustan-Smith, Richard C Harvey, Cheryl L Willman, Fady M Mikhail, Julia Meyer, Andrew J Carroll, Richard T Williams, Jinjun Cheng, Nyla A Heerema, Giuseppe Basso, Andrea Pession, Ching-Hon Pui, Susana C Raimondi, Stephen P Hunger, James R Downing, William L Carroll, Karen R Rabin.
Abstract
Aneuploidy and translocations are hallmarks of B-progenitor acute lymphoblastic leukemia (ALL), but many individuals with this cancer lack recurring chromosomal alterations. Here we report a recurring interstitial deletion of the pseudoautosomal region 1 of chromosomes X and Y in B-progenitor ALL that juxtaposes the first, noncoding exon of P2RY8 with the coding region of CRLF2. We identified the P2RY8-CRLF2 fusion in 7% of individuals with B-progenitor ALL and 53% of individuals with ALL associated with Down syndrome. CRLF2 alteration was associated with activating JAK mutations, and expression of human P2RY8-CRLF2 together with mutated mouse Jak2 resulted in constitutive Jak-Stat activation and cytokine-independent growth of Ba/F3 cells overexpressing interleukin-7 receptor alpha. Our findings indicate that these two genetic lesions together contribute to leukemogenesis in B-progenitor ALL.Entities:
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Year: 2009 PMID： 19838194 PMCID： PMC2783810 DOI： 10.1038/ng.469
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330