MEF2C-dysregulated pediatric T-cell acute lymphoblastic leukemia is associated with CDKN1B deletions and a poor response to glucocorticoid therapy

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological disease in which multiple genetic abnormalities cooperate in the malignant transformation of T-lymphoid progenitors. Although in pediatric T-ALL, CDKN1B deletions occur in about 12% of the cases and represent one of the most frequent copy number alterations, neither their association with other genetic alterations nor the clinical characteristics of these patients have been determined yet. In this study, we show that loss of CDKN1B increased the prevalence of cell cycle regulator defects in immature T-ALL, usually only ascribed to CDKN2A/B deletions, and that CDKN1B deletions frequently coincide with expression of MEF2C, considered as one of the driving oncogenes in immature early T-cell precursor (ETP) ALL. However, MEF2C-dysregulation was only partially associated with the immunophenotypic characteristics used to define ETP-ALL. Furthermore, MEF2C expression levels were significantly associated with or may even be predictive of the response to glucocorticoid treatment.

Keywords:

• T-cell acute lymphoblastic leukemia
• CDKN1B deletion
• MEF2C dysregulation
• immunophenotype
• glucocorticoid response

Acknowledgements

The authors would like to thank all those people who conduct the routine diagnostic work-up of the patient samples, which forms the essential basis for our research projects.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at http://dx.doi.org/10.1080/10428194.2017.1312383.

Additional information

Funding

This work was supported by grants of the Anniversary Fund of the Austrian National Bank [No. 14444 to SS] and the Austrian Ministry of Science and Research [GEN-AU II, GZ 200.136/1-VI/1/2005 to SS] as well as by the St. Anna Kinderkrebsforschung.