We investigated MYB rearrangements (MYB-R) and the levels of MYB expression, in 331 pediatric and adult patients with T-cell acute lymphoblastic leukemia (T-ALL). MYB-R were detected in 17 cases and consisted of MYB tandem duplication (tdup) (=14) or TRB@-MYB (=3). As previously reported, TRB@-MYB was found only in children (1.6%) while MYB tdup occurred in both age groups, although it was slightly more frequent in children (5.2% vs 2.8%). Shared features of MYB-R T-ALL were a non-early T-cell precursor (ETP) phenotype, a high incidence of NOTCH1/FBXW7 mutations (81%) and CDKN2AB deletions (70.5%). Moreover, they mainly belonged to HOXA (=8), NKX2-1/2-2/TLX1 (=4), and TLX3 (=3) homeobox-related subgroups. Overall, MYB-R cases had significantly higher levels of MYB expression than MYB wild type (MYB-wt) cases, although high levels of MYB were detected in ~30% of MYB-wt T-ALL. Consistent with the transcriptional regulatory networks, cases with high MYB expression were significantly enriched within the TAL/LMO subgroup (P = 0.017). Interestingly, analysis of paired diagnosis/remission samples demonstrated that a high MYB expression was restricted to the leukemic clone. Our study has indicated that different mechanisms underlie MYB deregulation in 30-40% of T-ALL and highlighted that, MYB has potential as predictive/prognostic marker and/or target for tailored therapy. This article is protected by copyright. All rights reserved.
MYB rearrangements and over-expression in T-cell acute lymphoblastic leukemia / Bardelli, Valentina; Arniani, Silvia; Pierini, Valentina; Pierini, Tiziana; Di Giacomo, Danika; Gorello, Paolo; Moretti, Martina; Pellanera, Fabrizia; Elia, Loredana; Vitale, Antonella; Storlazzi, Clelia Tiziana; Tolomeo, Doron; Mastrodicasa, Elena; Caniglia, Maurizio; Chiaretti, Sabina; Ruggeri, Loredana; Roti, Giovanni; Schwab, Claire; Harrison, Christine J; Almeida, André; Pieters, Tim; Van Vlierberghe, Pieter; Mecucci, Cristina; La Starza, Roberta. - In: GENES, CHROMOSOMES & CANCER. - ISSN 1045-2257. - (2021). [10.1002/gcc.22943]
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