Moreover, SHP1 phosphatase appears to be downregulated in non-responding CML patients and TKIs resistant cell lines, strongly limiting its interaction and regulation of SHP2 phosphatase activity, which has already been implicated in TKI resistance when its interaction domain on GAB2 is mutated [138]. This evidence concerns the gene PTPN6 and chronic myelogenous leukemia, BCR-ABL1 positive.