TY - JOUR
T1 - The Future of Targeting FLT3 Activation in AML
AU - Leick, Mark B.
AU - Levis, Mark J.
N1 - Funding Information:
Mark B. Leick declares no potential conflicts of interest. Mark J. Levis reports grants from Novartis and Astellas and consultancies for Novartis and Daiichi-Sankyo.
Publisher Copyright:
© 2017, Springer Science+Business Media New York.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Internal tandem duplications (ITD) and tyrosine-kinase domain (TKD) mutations of the FMS-like tyrosine-kinase 3 (FLT3) can be found in up to one third of patients with acute myeloid leukemia (AML) and confer a poor prognosis. First discovered 20 years ago, these mutations were identified as viable therapeutic targets, and FLT3 tyrosine-kinase inhibitors (TKIs) have been in development for the last decade with steadily increasing potency. However, FLT3-mutated AML often acquires resistance to the growing armamentarium of FLT3 inhibitors through a variety of mechanisms. In this review, we discuss the distinct clinical phenotype of FLT3-mutated AML, historically and currently available therapeutics, mechanisms of resistance, ongoing trials, and future outlook at treatment strategies.
AB - Internal tandem duplications (ITD) and tyrosine-kinase domain (TKD) mutations of the FMS-like tyrosine-kinase 3 (FLT3) can be found in up to one third of patients with acute myeloid leukemia (AML) and confer a poor prognosis. First discovered 20 years ago, these mutations were identified as viable therapeutic targets, and FLT3 tyrosine-kinase inhibitors (TKIs) have been in development for the last decade with steadily increasing potency. However, FLT3-mutated AML often acquires resistance to the growing armamentarium of FLT3 inhibitors through a variety of mechanisms. In this review, we discuss the distinct clinical phenotype of FLT3-mutated AML, historically and currently available therapeutics, mechanisms of resistance, ongoing trials, and future outlook at treatment strategies.
KW - Acute myeloid leukemia (AML)
KW - FLT3
KW - Tyrosine-kinase inhibitor (TKI)
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U2 - 10.1007/s11899-017-0381-2
DO - 10.1007/s11899-017-0381-2
M3 - Review article
C2 - 28421420
AN - SCOPUS:85017589303
SN - 1558-8211
VL - 12
SP - 153
EP - 167
JO - Current Hematologic Malignancy Reports
JF - Current Hematologic Malignancy Reports
IS - 3
ER -