Toll-like receptor (TLR) genes encode important components of innate immune system which is believed to play a role in the pathophysiology of myelodysplastic syndromes(MDS). Various TLR isoforms have been shown to be overexpressed in bone marrow CD34+ cells in MDS. In addition, the TLR2 p.F217S has been reported in approximately 10% of MDS patients. This variant is associated with enhanced activation of downstream signaling including NF-κB activity. TLR2 p.F217S may be associated with a higher frequency of chromosome 7 deletion in MDS as well. It is important to note that the TLR2 p.F217S variant has not been clearly established as a somatic variant and it is reported in the ESP database with an overall allele frequency of approximatly 0.3%. The potenital role of therapeutic targeting of TLR2 in MDS remains to be established.