FLT3 mutations are associated with other molecular lesions in AML.
The basic molecular defects underlying acute myeloid leukemias (AML) seem to be caused by inactivating mutations in transcription factors which control normal myeloid differentiation (Class II mutations) and genetic lesions in tyrosine kinases resulting in constitutive activation (Class I mutations). We sought to determine the frequency of associated mutations (Class I + Class II) in a consecutive series of adult de novo AML (353 patients) in order to stress the validity of this model. Mutations and rearrangements at the FLT3, AML1/ETO, CBFbeta/MYH11, AML1, CEBPalpha and MLL genes were investigated using standard molecular methods. Despite the limitations of the study (DNA availability hampered c-kit and ras mutational analysis), 3.4% of patients showed Class I + Class II mutations. Our findings could be consistent with the cooperative model. The search for new tyrosine kinases which can be the target of molecular lesions in AML warrants further investigation.
Carnicer
Maria J
MJ
Laboratori d'Hematologia, Hospital de la Santa Creu i Sant Pau, Avda Sant Antoni M Claret, 167, 08025 Barcelona, Spain.
Nomdedéu
Josep F
JF
Lasa
Adriana
A
Estivill
Camino
C
Brunet
Salut
S
Aventín
Anna
A
Sierra
Jorge
J
D000208:Acute Disease; D000328:Adult; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D020440:Gene Duplication; D015973:Gene Expression Regulation, Leukemic; D015321:Gene Rearrangement; D011905:Genes, ras / Q000235:genetics; D006579:Heterozygote; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D051788:Myeloid-Lymphoid Leukemia Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011519:Proto-Oncogenes; D012334:RNA, Neoplasm / Q000032:analysis; D000075142:RUNX1 Translocation Partner 1 Protein; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D051941:fms-Like Tyrosine Kinase 3
C107844:AML1-ETO fusion protein, human; C095514:CBFbeta-MYH11 fusion protein; D022763:CCAAT-Enhancer-Binding Protein-alpha; D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; D000075142:RUNX1 Translocation Partner 1 Protein; C493728:RUNX1 protein, human; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; C497970:FLT3 protein, human; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3