FLT3 mutations in a 10 year consecutive series of 177 childhood acute leukemias and their impact on global gene expression patterns.
During 1995-2004, 209 children/adolescents were diagnosed with acute lymphoblastic or myeloid leukemia (ALL, AML) in Southern Sweden, of which 177 (85%), comprising 128 B-lineage ALL, 34 AML, and 15 T-cell ALL, could be analyzed for internal tandem duplications (ITD) and activating point mutations in the second tyrosine kinase domain (ATKD) of FLT3. Seventeen (10%) FLT3 mutations (6 ITD, 11 ATKD; mutually exclusive) were detected. None of the T-cell ALL harbored any mutations. ITD and ATKD were found in 2% and 6% of the B-lineage ALL and in 12% and 9% of the AML, being particularly common in high hyperdiploid ALL (14%), ALL (20%), and AML (23%) with 11q23/MLL rearrangements, and in AML with a normal karyotype (60%). All ATKD-positive AML with MLL rearrangements harbored the t(9;11)(p21;q23). Global gene expression data were available for 76 of the B-lineage ALL and 19 of the AML, of which 6 (8%) and 3 (16%) had FLT3 mutations, respectively. No distinct expression pattern associated with FLT3 mutations was identified.
Andersson
Anna
A
Department of Clinical Genetics, University Hospital, Lund, Sweden. anna.andersson@med.lu.se
Paulsson
Kajsa
K
Lilljebjörn
Henrik
H
Lassen
Carin
C
Strömbeck
Bodil
B
Heldrup
Jesper
J
Behrendtz
Mikael
M
Johansson
Bertil
B
Fioretos
Thoas
T
D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000502:physiology*; D005787:Gene Frequency; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology / Q000235:genetics*; D008297:Male; D009154:Mutation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000235:genetics*; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3