A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer.

Tyrosine kinase inhibitors (TKIs) elicit high response rates among individuals with kinase-driven malignancies, including chronic myeloid leukemia (CML) and epidermal growth factor receptor-mutated non-small-cell lung cancer (EGFR NSCLC). However, the extent and duration of these responses are heterogeneous, suggesting the existence of genetic modifiers affecting an individual's response to TKIs. Using paired-end DNA sequencing, we discovered a common intronic deletion polymorphism in the gene encoding BCL2-like 11 (BIM).

Maintenance therapy with imatinib appears necessary despite molecular remission in FIP1L1-PDGFRA fusion gene positive hypereosinophilic disorder.

Patients with primary hypereosinophilic disorders who are positive for the FIP1L1-PDGFRA fusion gene mutation are highly responsive to therapy with imatinib mesylate. A 35-year-old man with FIP1L1-PDGFRA positive hypereosinophilic syndrome and cardiac involvement, was treated with imatinib 100 mg daily. Hematologic and molecular remission and reversal of end-organ damage was achieved.