Rearrangement of CRLF2 in B-progenitor-and Down syndrome-associated acute lymphoblastic leukemia

Academic Article

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. © 2009 Nature America, Inc. All rights reserved.
  • Published In

  • Nature Genetics  Journal
  • Digital Object Identifier (doi)

    Author List

  • Mullighan CG; Collins-Underwood JR; Phillips LAA; Loudin MG; Liu W; Zhang J; Ma J; Coustan-Smith E; Harvey RC; Willman CL
  • Start Page

  • 1243
  • End Page

  • 1246
  • Volume

  • 41
  • Issue

  • 11