Journal
GENES CHROMOSOMES & CANCER
Volume 60, Issue 7, Pages 482-488Publisher
WILEY
DOI: 10.1002/gcc.22943
Keywords
MYB expression; MYB tandem duplication; T-ALL; T-cell acute lymphoblastic leukemia; TRB-MYB
Categories
Funding
- Associazione Italiana per la Ricerca sul Cancro [IG-15525]
- Blood Cancer UK
- Comitato per la vita Daniele Chianelli, Perugia
- Fondazione Cassa Di Risparmio Perugia [2018.0418.021]
- Fund Baillet Latour
- PRIN [2017PPS2X4]
- Research Foundation Flanders (FWO)
- Sergio Luciani Association, Fabriano
- Societa Italiana di Ematologia Sperimentale
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The study investigated MYB rearrangements and expression levels in pediatric and adult patients with T-cell acute lymphoblastic leukemia. It found that cases with MYB rearrangements had higher levels of MYB expression, were associated with non-ETP phenotype, and mainly belonged to specific homeobox-related subgroups. This suggests the potential of MYB as a predictive/prognostic marker and/or target for tailored therapy in 30-40% of T-ALL cases.
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 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 similar to 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.
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