C-Kit、NPM1and FLT3Gene Mutations And MLL-PTD Patterns And Their Prognostic Impact On Patients With Acute Myeloid Leukemia In China

Objective To evaluate the prevalence and distribution of C-Kit, NPM₁and FLT3gene mutations and MLL partial tandem duplication for patients with acute myeloidleukemia （AML）, and to analyze the relationship between the genemutations/duplication and their prognosis.Methods The C-Kit gene in exon8and17, NPM₁gene in exon12, FLT3-TKDgene in exon20, FLT3-ITD gene in exon14/15were detected by direct sequencing.MLL partial tandem duplication was detected by RT-PCR. Clinical data was collectedand followed up if the patient had accepted treatment in our hospital.Results: Among the656AML patients, C-Kit exon8mutations were found in6patients （0.9%）, C-Kit exon17in33（5.0%）, NPM₁in169（25.8%）, FLT3-TKD in46（7.1%）, FLT3-ITD in178（27.1%）.6subtypes of mutations were detected in C-Kitexon8mutations.8subtypes were detected in C-Kit exon17.11subtypes were detectedin FLT3-TKD.15subtypes were detected in NPM₁mutations, of which5subtype werenot reported before. C-Kit exon17mutations were more frequently detected in patientswith t（8;21） and exon8in patients with inv（16） cytogenetic abnormal. No genemutations except FLT3were detected in M₃patients. NPM₁and FLT3-ITD mutationswere often detected in individuals with cytogenetic normalities or M₅and M₁of FABclassification, and accompanied higher white blood cell counts in peripheral blood,higher blast counts in bone marrow and low CD34expression. The older the patientswere when diagnosed, the more gene mutations, the higher white blood count wasdetected. More mutations were found in individuals with normal karyotype than withother karyotypes. It appeared that FLT3-ITD was significantly associated with shorteroverall survival （p=0.004）, NPM₁was not significantly associated with OS. But NPM₁+/ITD-patients were of longer OS. MLL-PTD did not coexist with specificaberrations and mutations, except FLT3-ITD, and confered a worse prognosis（p=0.013）.Conclusions Our results showed that the mutations type and counts had particlardistribution in MICM subtypes, and were associated with white blood counts inperipheral blood, blast counts in bone marrow and prognosis. MLL-PTD hadassociation with normal karyotype and FLT3-ITD, and confered shorter overall survial.