The duplication of MYB, a gene encoding for a transcription factor, can be used in the molecular phenotyping of T-cell acute lymphoblastic leukemia (T-ALL) patients. The knock-down of MYB expression or the biochemical inhibition of MYB leads to T-ALL cell line differentiation and can be exploited therapeutically.
Summary of the invention
T-ALL is an aggressive T-cell malignancy that is most common in children and adolescents. VIB scientists identified a duplication of the MYB oncogene in a subset of T-ALL patients. This duplication is associated with a 3-fold increase in MYB expression. MYB overexpression is known to impair hematopoetic differentiation.
Moreover inhibition of MYB in combination with the inhibition of NOTCH1 signaling through a γ-secretase inhibitor results in a strong synergistic effect on proliferation and viability of malignant cells.
- MYB duplication can be used for patient stratification in T-ALL in the context of therapy or selection of clinical trial subjects
- Inhibitory compounds against MYB promise to allow therapeutic intervention in T-ALL
- A synergistic effect between MYB inhibition and NOTCH1 inhibition can be therapeutically exploited through lower dosing regimes