BRAF and melanoma: For example, in melanoma, heterogeneous, stochastic expression of BRAF inhibitor resistance markers enables the initial survival of a subpopulation of cells, which also has the necessary epigenetic plasticity required to undergo transcriptional adaptation and form a stably resistant population.31 We also observed similar results in our model of BET inhibitor resistance in AML:29,30 although not intrinsically resistant, the drug-naïve leukaemic granulocyte macrophage progenitor population enriched for leukaemia stem cells showed a greater capacity to adapt than the bulk population.