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- Title
Rearrangement of CRLF2 in B-progenitor– and Down syndrome–associated acute lymphoblastic leukemia.
- Authors
Mullighan, Charles G.; Collins-Underwood, J. Racquel; Phillips, Letha A. A.; Loudin, Michael G.; Wei Liu; Jinghui Zhang; Jing Ma; Coustan-Smith, Elaine; Harvey, Richard C.; Willman, Cheryl L.; Mikhail, Fady M.; Meyer, Julia; Carroll, Andrew J.; Williams, Richard T.; Jinjun Cheng; Heerema, Nyla A.; Basso, Giuseppe; Pession, Andrea; Ching-Hon Pui; Raimondi, Susana C.
- 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.
- Subjects
LYMPHOBLASTIC leukemia; DOWN syndrome; ANEUPLOIDY; CYTOKINES; LEUKEMIA etiology
- Publication
Nature Genetics, 2009, Vol 41, Issue 11, p1243
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.469