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MYB rearrangements and over-expression in T-cell acute lymphoblastic leukemia

Lookup NU author(s): Claire Schwab

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Abstract

© 2021 Wiley Periodicals LLCWe 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 T cell receptor beta locus (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 =.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.


Publication metadata

Author(s): Bardelli V, Arniani S, Pierini V, Pierini T, Di Giacomo D, Gorello P, Moretti M, Pellanera F, Elia L, Vitale A, Storlazzi CT, Tolomeo D, Mastrodicasa E, Caniglia M, Chiaretti S, Ruggeri L, Roti G, Schwab C, Harrison CJ, Almeida A, Pieters T, Van Vlierberghe P, Mecucci C, La Starza R

Publication type: Article

Publication status: Published

Journal: Genes Chromosomes and Cancer

Year: 2021

Pages: epub ahead of print

Online publication date: 20/02/2021

Acceptance date: 19/02/2021

ISSN (print): 1045-2257

ISSN (electronic): 1098-2264

Publisher: Blackwell Publishing Inc.

URL: https://doi.org/10.1002/gcc.22943

DOI: 10.1002/gcc.22943

PubMed id: 33611795


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