We verified this hypothesis in vivo in a PDX model using immunodeficient NSG mice as hosts bearing primary CD34+ CML cells resistant to imatinib and dasatinib and carrying a pathogenic variant of a gain-of-function mutation in the PTPN11 gene (Gly60Val/c.179G > T) but not mutations within the kinase domain of BCR-ABL1, as identified by NGS analysis of samples from the clinical resistance time point. Here, CD34 is linked to chronic myelogenous leukemia, BCR-ABL1 positive.