XL P2RY8 del detects deletions in the short arm of chromosome X and Y at Xp22.33 and Yp11.32, respectively. The orange labeled probe spans P2RY8 and extends distally, the green labeled probe covers the 5´end of P2RY8 and extends proximally.

Probe maps are created in accordance with the intended purpose of the product. Solid colored bars do not necessarily indicate that the probe fully covers the indicated genomic region. Therefore, caution is advised when interpreting results generated through off-label use. Probe map details based on UCSC Genome Browser GRCh37/hg19. Map components not to scale. Further information is available on request.

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children (prevalence of approximately 1:1500). Children with Down syndrome have a 10- to 20-fold increased risk of developing acute leukemia. B-Cell dependent BCR-ABL1-like ALL, also known as Philadelphia chromosome (Ph)-like ALL, is a high-risk subset with a gene expression profile which shares significant overlap with that of Ph-positive (Ph+) ALL, but lacking the BCR-ABL1 fusion. In 2017, the WHO recognized BCR-ABL1-like ALL as new entity.
Chromosomal rearrangements resulting in the overexpression of cytokine receptor like factor 2 (CRLF2) can be found in up to 50% of BCR-ABL1-like ALL cases. The CRLF2 gene is located in the pseudoautosomal region 1 (PAR1) of the X and the Y chromosome. CRLF2 rearrangements result in increased protein levels, which initiate significantly enhanced JAK/STAT signaling, whereby disproportionate JAK and subsequent STAT5 activation induces strongly enhanced B-cell activation and proliferation. One of the genetic mechanisms leading to constitutive overexpression of CRLF2 is a gene fusion of CRLF2 with another PAR1 gene, purinergic receptor P2Y8 (P2RY8). The resulting P2RY8-CRLF2 fusion under the control of the P2RY8 promoter is strongly transcribed in lymphoid cells.
XL P2RY8 del can be used to detect the presence of the P2RY8-CRLF2 fusion gene.

Clinical Applications

• Acute Lymphoblastic Leukemia (ALL)

XL P2RY8 del hybridized to bone marrow cells. One aberrant cell of a patient with a gonosomal constellation of XXY is shown. The two orange-green fusion signals represent the two unaffected CRLF2P2RY8 loci. A deletion between CRLF2 and P2RY8 is identified by a separate green signal. This signal pattern gives strong indication that the P2RY8-CRLF2 gene-fusion is present.

• Mullighan et al (2009) Nat Genet 41:1243-1246
• Russell et al (2017) Genes Chromosomes Cancer 56:363-372
• Tasian et al (2017) Blood 130:2064-2072