Diagnosis and Treatment of T-Cell Acute Lymphoblastic Leukemia using MYB

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.

Application

  • 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
 
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