Longitudinal Multilevel Omic Analysis of Pediatric T-ALL Reveals Distinct Mechanisms for Disease Progression in Type 1 and in Type 2 Relapses

We aimed at understanding the relapse-driving processes in pediatric T-ALL and performed an integrated longitudinal multi-level omics analysis of 13 T-ALL patients at initial diagnosis (INI) and relapse (REL). We compared the mutation (SNV/InDels) and copy number alteration (CNA) patterns as well as...

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Published in:Blood 2018-11, Vol.132 (Supplement 1), p.2826-2826
Main Authors: Richter-Pechanska, Paulina, Kunz, Joachim B., Rausch, Tobias, Erarslan-Uysal, Busra, Bornhauser, Beat, Frismantas, Viktoras, Dobay, Maria Pamela, Von Knebel Doeberitz, Caroline, Zimmermann, Martin, Fuhrmann, Stephan, Stanulla, Martin, Schrappe, Martin, Cario, Gunnar, Escherich, Gabriele, Bakharevich, Kseniya, Kirschner-Schwabe, Renate, Eckert, Cornelia, Pfister, Stefan, Muckenthaler, Martina U., Bourquin, Jean-Pierre, Korbel, Jan O., Kulozik, Andreas E.
Format: Article
Language:English
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Summary:We aimed at understanding the relapse-driving processes in pediatric T-ALL and performed an integrated longitudinal multi-level omics analysis of 13 T-ALL patients at initial diagnosis (INI) and relapse (REL). We compared the mutation (SNV/InDels) and copy number alteration (CNA) patterns as well as gene expression, methylation levels and chromatin accessibility by ATAC-Seq. Aberrant expression of T-ALL transcription factors (TAL1, TAL2,LMO2, TLX1, TLX3, NKX2.4 and NKX2.5) was preserved from initial presentation to relapse in all patients. These leukemia-driving events defined the expression patterns, methylation profiles and the chromatin accessibility landscapes. A global differential analysis of the RNA-Seq data (DESeq2, padj
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2018-99-117978