Pharmaceutical inhibition of BCL6 ameliorates resistance to imatinib in chronic myeloid leukemia

Abstract

The tyrosine kinase inhibitors (TKIs) have improved overall survival of CML (chronic myeloid leukemia) patients and allow them to experience normal life expectancy. However, relapse and drug resistance remain the main challenges in the clinical treatment of CML. The B-cell lymphoma 6 (BCL6) is essential to regulation of multiple function such as immune response and lymphomagenesis in lymph node germinal cells. Recent studies have shown that BCL6 is required for the maintenance of leukemia stem cells in CML, but the expression of Bcl-6 in response to Imatinib and the underlying mechanism are still unclear. Here, we found that BCL6 is expressed at high levels in primary CML bone marrow samples and CML TKI-resistance cell lines. CML cells with higher levels of BCL6 were generally sensitive to treatment with BCL6 inhibitors, BI-3812. Treatment of CML cells with BCL6 inhibitor and TKIs suggested enhanced anti-leukemia activity. In summary, our findings suggest BCL6 as a therapeutic target for the treatment of CML.

Keywords

• Chronic myeloid leukemia
• Resistance
• Imatinib
• BI-3812
• Bcl6 inhibitor