Conducting genome-wide DNA methylation profiling in these models [MafB in multiple myeloma (MM) (Vicente-Duenas et al., 2012), Bcl6 in Diffuse Large B cell Lymphoma (DLBCL) (Green et al., 2014), BCR-ABLp210 in chronic myeloid leukemia (CML) (Perez-Caro et al., 2009)] it has been identified a molecular reprogramming profile in the tumor-initiating cells (the hematopoietic stem/progenitor cells (HS/PC)), where the oncogene was expressed, that was still present in the tumor cells where the oncogene was switched off. The gene discussed is BCR; the disease is diffuse large B-cell lymphoma.