@article{374f32ba661c4fc6b53a2bcdc030c040,
title = "Rearrangement of CRLF2 in B-progenitor-and Down syndrome-associated acute lymphoblastic leukemia",
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.",
author = "Mullighan, {Charles G.} and Collins-Underwood, {J. Racquel} and Phillips, {Letha A.A.} and Loudin, {Michael G.} and Wei Liu and Jinghui Zhang and Jing Ma and Elaine Coustan-Smith and Harvey, {Richard C.} and Willman, {Cheryl L.} and Mikhail, {Fady M.} and Julia Meyer and Carroll, {Andrew J.} and Williams, {Richard T.} and Jinjun Cheng and Heerema, {Nyla A.} and Giuseppe Basso and Andrea Pession and Pui, {Ching Hon} and Raimondi, {Susana C.} and Hunger, {Stephen P.} and Downing, {James R.} and Carroll, {William L.} and Rabin, {Karen R.}",
note = "Funding Information: We thank M. Wang and D. Naeve (Functional Genomics Laboratory, Hartwell Center, St. Jude Children{\textquoteright}s Research Hospital) for conducting array-CGH analysis; E. Walker and J. Morris (CACT Laboratory, Hartwell Center) for conducting SNP microarrays; S. Tate, J. Armstrong and K. Rakestraw (St. Jude Hartwell Center Sequencing Core) for conducting sequencing; the St. Jude Flow Cytometry Core; John Gray and the St. Jude Vector Core for lentiviral reagents and methods; the St. Jude Tissue Resources Laboratory for providing primary patient samples; S. Nutt for providing the MSCV-mIL7R-IRES-hCD4 retroviral vector; G.P. Nolan, Stanford University, for the Eco Phoenix packaging cells (http://www.stanford.edu/group/nolan); and M. Smith and K. Dobbin for gene expression studies of CRLF2. This work was supported by National Cancer Institute Cancer Center Support Grant P30 CA021765, the American Lebanese Syrian Associated Charities of St. Jude Children{\textquoteright}s Research Hospital, a Bear Necessities Pediatric Research Foundation grant (to K.R.R.), a Children{\textquoteright}s Cancer Research Foundation grant (to K.R.R.) and National Institutes of Health Pediatric Oncology Clinical Research Training Grant CA90433-06 (to K.R.R.).",
year = "2009",
month = nov,
doi = "10.1038/ng.469",
language = "English (US)",
volume = "41",
pages = "1243--1246",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "11",
}