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]. Here, PTPN11 is linked to chronic myelogenous leukemia, BCR-ABL1 positive.