Activating FLT3 mutations in CD117/KIT(+) T-cell acute lymphoblastic leukemias.
Activating FLT3 mutations are the most common genetic aberrations in acute myeloid leukemia (AML), resulting in the constitutive activation of this receptor tyrosine kinase (RTK), but such mutations are rarely found in acute lymphoblastic leukemia (ALL). Here we describe a unique subset of de novo adult T-cell ALL (T-ALL) cases that coexpress CD117/KIT and cytoplasmic CD3 (CD117/KIT(+) ALL). Activating mutations in the FLT3 RTK gene were found in each of 3 CD117/KIT(+) cases that were analyzed, but not in 52 other adult T-ALL samples from the same series that lacked CD117/KIT expression. Our results indicate the need for clinical trials to test the efficacy of drugs that inhibit the FLT3 RTK in this subset of patients with T-ALL.
Paietta
Elisabeth
E
Our Lady of Mercy Cancer Center-Immunology Laboratory, 600 East 233rd St, Bronx, NY 10466, USA. epaietta@earthlink.net
Ferrando
Adolfo A
AA
Neuberg
Donna
D
Bennett
John M
JM
Racevskis
Janis
J
Lazarus
Hillard
H
Dewald
Gordon
G
Rowe
Jacob M
JM
Wiernik
Peter H
PH
Tallman
Martin S
MS
Look
A Thomas
AT
D000595:Amino Acid Sequence; D015971:Gene Expression Regulation, Enzymologic; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D008969:Molecular Sequence Data; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000503:physiopathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D051941:fms-Like Tyrosine Kinase 3
D011518:Proto-Oncogene Proteins; C497970:FLT3 protein, human; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3