Mutational analysis of the KIT gene in myelodysplastic syndrome (MDS) and MDS-derived leukemia.
The progenitor cells of myelodysplastic syndrome (MDS) are thought to undergo a multistep process during their transformation into overt acute leukemia. In this study, the role of mutation of the KIT gene in the extracellular membrane, juxtamembrane and tyrosine kinase domains was investigated in 75 patients with MDS or MDS-derived leukemia (MDS-AML). Mutation was detected in 2 of 15 (13.3%) patients with refractory anemia with excess blasts transformation (RAEB-T), in 1 of 15 (6.6%) patients with chronic myelomonocytic leukemia (CMML), and in 5 of 26 (19.2%) patients with MDS-AML. However, no mutation was found in any of the nine patients with refractory anemia (RA) or the 10 patients with refractory anemia with excess blasts (RAEB). Of the mutations, five patients had changes at the same codon in tyrosine kinase domain, Asp816, while the remainder had unique mutations. These observations suggest that KIT gene mutations identified in the advanced stage of MDS, and genetic abnormality in the KIT gene, particularly at codon 816, might be additional events that contribute to the progression of MDS to AML.
Lorenzo
Felipe
F
Division of Hematology and Oncology, Mie University School of Medicine, Tsu, Mie, Japan.
Nishii
Kazuhiro
K
Monma
Fumihiko
F
Kuwagata
Shogo
S
Usui
Eiji
E
Shiku
Hiroshi
H
D000328:Adult; D000368:Aged; D000754:Anemia, Refractory, with Excess of Blasts / Q000235:genetics; D001853:Bone Marrow / Q000473:pathology*; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D007564:Japan; D007621:Karyotyping; D007938:Leukemia / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000503:physiopathology; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D003062:Codon; D019009:Proto-Oncogene Proteins c-kit