We show that (i) AZA and DAC limit the release of all NKG2DL in the supernatants of AML cell lines; (ii) decreased levels of sNKG2DL prevent the downregulation of the NKG2D receptor and favor the recognition and lysis of AML cells by NKL cells; (iii) ADAM17 is the sheddase involved in the release of sNKG2DL in AML cell lines; (iv) demethylation of TIMP3 gene may be responsible for the lower level of shedding of MICA, MICB and ULBP2 in AML cells; and (v) high TIMP3 DNA methylation levels in AML patients are associated with an adverse cytogenetic prognosis for the disease. The gene discussed is ADAM17; the disease is acute myeloid leukemia.