T-cell acute lymphoblastic leukemia (T-ALL) is a rare but aggressive subtype of leukemia affecting the T-cell lineage During the malignant transformation of T-cells, a clonal expansion of immature cells is selected for via the gradual accumulation of advantageous epigenetic changes and genetic mutations Long-lived pre-leukemic stem cells (pre-LSCs) were uncovered as an initiating event in various bloodborn cancers, recently also in mouse models of T-ALL pre-LSC look phenotypically normal, but are molecularly poised to transform They able to differentiate into functional mature blood cells but have also retained their stem cell properties, allowing clonal expansion and subsequent acquisition of extra oncogenic driver mutations, eventually leading to the onset of a full-blown leukemia TET2, an enzyme that catalyze the DNA demethylation, has previously been shown to play pivotal roles in regulating the aberrant self-renewal of pre-LSCs Here we will investigate the roles of TET2, and DNA demethylation, in the development of T-ALL In addition, we will

evaluate the potential of demethylating agents as a therapeutic strategy for the treatment of this aggressive leukemia