Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jul;60(7):482-488.
doi: 10.1002/gcc.22943. Epub 2021 Mar 8.

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

Valentina Bardelli  1 , Silvia Arniani  1 , Valentina Pierini  1 , Tiziana Pierini  1 , Danika Di Giacomo  1 , Paolo Gorello  1 , Martina Moretti  1 , Fabrizia Pellanera  1 , Loredana Elia  2 , Antonella Vitale  2 , Clelia Tiziana Storlazzi  3 , Doron Tolomeo  3 , Elena Mastrodicasa  4 , Maurizio Caniglia  4 , Sabina Chiaretti  2 , Loredana Ruggeri  1 , Giovanni Roti  5 , Claire Schwab  6 , Christine J Harrison  6 , André Almeida  7 , Tim Pieters  7 , Pieter Van Vlierberghe  7 , Cristina Mecucci  1 , Roberta La Starza  1
Affiliations

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

Valentina Bardelli et al. Genes Chromosomes Cancer. 2021 Jul.

Abstract

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 ~ 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.

Keywords: MYB expression; MYB tandem duplication; T-ALL; T-cell acute lymphoblastic leukemia; TRB-MYB.

PubMed Disclaimer

References

REFERENCES

    1. Liu X, Xu Y, Han L, Yi Y. Reassessing the potential of Myb-targeted anti-cancer therapy. J Cancer. 2018;9(7):1259-1266. https://doi.org/10.7150/jca.23992.
    1. Pattabiraman DR, Gonda TJ. Role and potential for therapeutic targeting of MYB in leukemia. Leukemia. 2013;27(2):269-277. https://doi.org/10.1038/leu.2012.225.
    1. Ramsay RG, Gonda TJ. MYB function in normal and cancer cells. Nat Rev Cancer. 2008;8(7):523-534. https://doi.org/10.1038/nrc2439.
    1. Thomas MD, Kremer CS, Ravichandran KS, Rajewsky K, Bender TP. C-Myb is critical for B cell development and maintenance of follicular B cells. Immunity. 2005;23(3):275-286. https://doi.org/10.1016/j.immuni.2005.08.005.
    1. Nakano K, Uchimaru K, Utsunomiya A, Yamaguchi K, Watanabe T. Dysregulation of c-Myb pathway by aberrant expression of proto-oncogene MYB provides the basis for malignancy in adult T-cell leukemia/lymphoma cells. Clin Cancer Res. 2016;22(23):5915-5928. https://doi.org/10.1158/1078-0432.CCR-15-1739.

Publication types

MeSH terms

LinkOut - more resources