The existence of other factors that determine HHT activity is clear based on its effectiveness against CML, which lacks mutations in VHL. However, our preclinical evaluation and validation of the synthetic lethality of HHT with VHL mutation in two tumorgraft lines represents proof-of-principle that this screening strategy can successfully identify compounds that may be useful clinically. The gene discussed is VHL; the disease is chronic myelogenous leukemia, BCR-ABL1 positive.