High-dose nicotinamide, a histone deacetylase inhibitor (Sirtuin-1), can prevent emergence of treatment resistance in chronic myeloid leukemia – A perspective

Abstract

Chronic myeloid leukemia (CML) is now widely treated using tyrosine kinase inhibitors (TKI). These TKIs can annihilate dividing cells, but they have no effect on quiescent stem cells. These quiescent stem cells slowly give rise to treatment resistance in the form of mutations. T315I is one such mutation that is resistant to most of the TKI’s and treating this acquired kinase domain mutation i.e T315I, is often costly. Nicotinamide is histone deacetylase inhibitor. It inhibits SIRT-1(Sirtuin-1). High dose nicotinamide, when used with TKI, will not only potentiate TKI action, but also annihilate quiescent stem cells thereby preventing the emergence of treatment resistance in CML. We propose a perspective article on using high dose nicotinmaide along with TKI to prevent emergence of treatment resistance. Thus going by the famous idiom “prevention is better than cure”,we suggest trial on high dose nicotinamide with TKI in CML.