Role of mutation independent constitutive activation of FLT3 in juvenile myelomonocytic leukemia.
FLT3 gene mutations have been identified as prognostic factors in myeloid malignancies. Furthermore, FLT3 can be activated by wild type overexpression or ligand-dependent in leukemic cells co-expressing FLT3 ligand (FLT3L). So far no data are available on FLT3/FLT3L expression and activation in JMML. In 51 clinical JMML samples, activating mutations were screened, FLT3 and FLT3L mRNA levels were assessed and the sensitivity of JMML cells to the FLT3 inhibitor PKC412 was tested by MTT assays. No evidence for constitutively activation of FLT3/FLT3L was found in JMML, indicating that FLT3 inhibitors are unlikely to be effective in JMML.
de Vries
Andrica C H
AC
ErasmusMC-Sophia Children's Hospital, Department of Pediatric Hematology/Oncology, Room Sp 2568, Dr. Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands.
Stam
Ronald W
RW
Schneider
Pauline
P
Niemeyer
Charlotte M
CM
van Wering
Elisabeth R
ER
Haas
Oskar A
OA
Kratz
Christian P
CP
den Boer
Monique L
ML
Pieters
Rob
R
van den Heuvel-Eibrink
Marry M
MM
D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D054429:Leukemia, Myelomonocytic, Juvenile / Q000201:enzymology / Q000209:etiology*; D012333:RNA, Messenger / Q000032:analysis; D019311:Staurosporine / Q000031:analogs & derivatives / Q000494:pharmacology; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; D019311:Staurosporine; C059539:midostaurin