Tyrosine Kinase Inhibitors in Pulmonary Vascular Disease

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder, characterized by proliferation of granulocytes, caused by a translocation that produces the Philadelphia chromosome resulting in constitutively active BCR-ABL tyrosine kinase. Imatinib and dasatinib are 2 BCR-ABL tyrosine kinase inhibitors (TKI) used in the treatment of CML. Since the introduction of dasatinib earlier this decade, more than 100 cases of dasatinib-induced pulmonary arterial hypertension PAH have been reported in Europe. When imatinib was introduced, no such increase in pulmonary vasculopathy was identified. In this perspective piece, the author discusses the work of Guignabert et al., recently published in the Journal of Clinical Investigation, which examined the mechanism through which dasatinib mediates its toxic pulmonary vascular effects.