| Title: |
Molecular variants, clonal evolution and clinical relevance in pediatric and adult T-cell lymphoblastic neoplasia. |
| Authors: |
Sandmann, Sarah; te Vrugt, Marcel; Randau, Gerrit; Beder, Thomas; Neumann, Martin; Lange, Toni; Alfert, Amelie; Mueller, Stephanie; Hotfilder, Marc; Rossi, Corinne; Eckert, Cornelia; Moericke, Anja; Horns, Johanna Maria; Zimmermann, Martin; Varghese, Julian; Brüggemann, Monika; Burkhardt, Birgit |
| Source: |
Blood Cancer Journal; 4/2/2026, Vol. 16 Issue 1, p1-6, 6p |
| Abstract: |
T-cell lymphoblastic lymphoma (T-LBL) and T-cell acute lymphoblastic leukemia (T-ALL) originate from thymic T-cell precursors, with ongoing debate on whether they are variants of the same disease or distinct entities. For 211 patients, including pediatric and adult T-ALL and T-LBL cases, targeted next-generation sequencing and SNP-arrays were performed, and single-nucleotide variants, indels and copy-number variants (CNVs) were analyzed. We aimed to assess genetic differences between T-ALL and T-LBL across age. Generally, mutational landscape analysis identified mutated PHF6 being associated with higher, NOTCH1 with lower age at diagnosis for both T-LBL and T-ALL. Association of CNVs with higher age was evident for T-ALL, but not T-LBL. Analysis of clonal evolution revealed that CNVs – especially deletions and LOH in chromosome 9 (LOH_in_9p) – were observed as first mutational event in both pediatric T-ALL and T-LBL. The sequence of genetic events, starting with LOH_in_9p followed by mutations in NOTCH1, was significantly more frequent in pediatric T-ALL and T-LBL. Detailed evaluation of the patients’ individual clonal evolution indicated that the proportion of malignant cells without NOTCHMT determines the risk of relapse (hazard ratio 1.032, p = 4.65*10−5). In T-ALL, aside from MRD, validated molecular markers for risk-group stratification remain limited. Our data suggest that molecular metrics analogous to those in T-LBL may help refining risk stratification in T-ALL as well. [ABSTRACT FROM AUTHOR] |
| : |
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| Database: |
Complementary Index |