Genomic and transcriptional landscape of P2RY8-CRLF2-positive childhood acute lymphoblastic leukemia

The mutational and transcriptional landscape of P2RY8-CRLF2-positive ALL was defined in 41 major clone fusion-positive cases including 19 matched diagnosis and relapse pairs by an integrated analysis of whole-exome and RNA sequencing. We detected a variety of frequently subclonal and highly unstable JAK/STAT but also RTK/Ras pathway activating mutations in 76% of cases at diagnosis and virtually all relapses. Unlike P2RAY8-CRLF2 that was lost in 32% of relapses, all other genomic deletions affecting lymphoid development and cell cycle remained stable. Only IKZF1 alterations predominated in relapsing cases and increased from initially 36 to 58% in matched cases. IKZF1¹s transcriptional signature revealed compromised stem cell features with signs of impaired lymphoid differentiation, enhanced focal adhesion, activated hypoxia pathway, deregulated cell cycle and increased drug resistance.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 1 Publication

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Dataset ID	Description	Technology	Samples
EGAD00001002666	Genomic DNA from leukemic and remission bone marrow mononuclear cells was isolated with the QIAamp DNA Blood Extraction Kit (Qiagen, Venlo, The Netherlands). Libraries were prepared using Nextera Rapid Capture Exome Kit (Illumina, San Diego, USA). Paired-end sequencing of 100 bp reads was performed on a HiSeq 2000 (Illumina) to obtain at least a 50 x coverage.		105

Publications	Citations
Genomic and transcriptional landscape of P2RY8-CRLF2-positive childhood acute lymphoblastic leukemia. Vesely C, Frech C, Eckert C, Cario G, Mecklenbräuker A, Zur Stadt U, Nebral K, Kraler F, Fischer S, Attarbaschi A, Schuster M, Bock C, Cavé H, von Stackelberg A, Schrappe M, Horstmann MA, Mann G, Haas OA, Panzer-Grümayer R. Leukemia 31: 2017 1491-1501	29