A phase-1 study of dasatinib plus all-trans retinoic acid in acute myeloid leukemia

• Published in: Leukemia & lymphoma Vol. 59; no. 11; pp. 2595 - 2601
• Main Authors: Redner, Robert L., Beumer, Jan H., Kropf, Patricia, Agha, Mounzer, Boyiadzis, Michael, Dorritie, Kathleen, Farah, Rafic, Hou, Jing-Zhao, Im, Annie, Lim, Seah H., Raptis, Anastasios, Sehgal, Alison, Christner, Susan M., Normolle, Daniel, Johnson, Daniel E.
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 02.11.2018
• Subjects: Acute Disease; Aged; Aged, 80 and over; AML; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; ATRA; dasatinib; Dasatinib - administration & dosage; Dasatinib - adverse effects; Dasatinib - pharmacokinetics; Drug Administration Schedule; Headache - chemically induced; Humans; Leukemia, Myeloid - drug therapy; Leukemia, Myeloid - metabolism; Leukemia, Myeloid - pathology; Long QT Syndrome - chemically induced; Middle Aged; pharmacodynamics; pharmacokinetics; phase I; src-Family Kinases - antagonists & inhibitors; src-Family Kinases - metabolism; Treatment Outcome; Tretinoin - administration & dosage; Tretinoin - adverse effects; Tretinoin - pharmacokinetics; AML; pharmacokinetics; phase I; dasatinib; ATRA; pharmacodynamics

Src family kinases (SFKs) are hyperactivated in acute myeloid leukemia (AML). SFKs impede the retinoic acid receptor, and SFK inhibitors enhance all-trans retinoic acid (ATRA)-mediated cellular differentiation in AML cell lines and primary blasts. To translate these findings into the clinic, we unde...