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Although some patients with newly diagnosed acute myeloid leukemia (AML) experience durable complete remission and cure with anthracycline plus cytarabine (AraC) induction therapy, most relapse and ultimately die from the disease. To explore mechanisms underlying treatment resistance, investigators performed RNA sequence analysis to identify differentially expressed genes in AraC-resistant and AraC-sensitive AML cells.
GLI1 (glioma-associated protein 1), a transcription factor for sonic hedgehog signaling, was elevated in AML cells resistant to AraC. AraC sensitivity could be restored by molecular knockdown of the GLA1 gene and by the sonic hedgehog inhibitor GDC-0449 at clinically achievable levels. A second protein, UGT1A (UDP glucuronosyl…