FLT3 mutations in childhood acute lymphoblastic leukemia.
Activating mutations of the FLT3 receptor tyrosine kinase are common in acute myelogenous leukemia (AML) but are rare in adult acute lymphoblastic leukemia (ALL). We have recently shown that FLT3 is highly expressed and often mutated in ALLs with rearrangement of the mixed lineage leukemia (MLL) gene on chromosome 11q23. Because hyperdiploid ALL samples also show high-level expression of FLT3, we searched for the presence of FLT3 mutations in leukemic blasts from 71 patients with ALL. The data show that approximately 25% (6 of 25) of hyperdiploid ALL samples possess FLT3 mutations, whereas only 1 of 29 TEL/AML1-rearranged samples harbored mutations (P =.04, Fisher exact test). Three mutations are novel in-frame deletions within a 7-amino acid region of the receptor juxtamembrane domain. Finally, 3 samples from patients whose disease would relapse harbored FLT3 mutations. These data suggest that patients with hyperdiploid or relapsed ALL might be considered candidates for therapy with newly described small-molecule FLT3 inhibitors.
Armstrong
Scott A
SA
Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115,USA.
Mabon
Meghann E
ME
Silverman
Lewis B
LB
Li
Aihong
A
Gribben
John G
JG
Fox
Edward A
EA
Sallan
Stephen E
SE
Korsmeyer
Stanley J
SJ
D002648:Child; D050676:Core Binding Factor Alpha 2 Subunit; D004252:DNA Mutational Analysis; D004171:Diploidy; D005820:Genetic Testing; D006801:Humans; D009154:Mutation; D015514:Oncogene Proteins, Fusion; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012008:Recurrence; D017384:Sequence Deletion; D051941:fms-Like Tyrosine Kinase 3; D000097764:ETS Translocation Variant 6 Protein
D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein; C497970:FLT3 protein, human