Effect Of Signal Transduction Pathway Gene Mutations On The First Induced Remission In Patients With CBF-AML And Its Clinical Characteristics

Objective:To investigate the effect of other gene mutations outside the fusion gene on the first complete remission?CR₁?induced by one course of induction chemotherapy in patients with core-binding factor-associated acute myeloid leukemia?CBF-AML?.Methods:1.Analysis of 34 Gene Mutations in Initial CBF-AML Patients.DNA was extracted from bone marrow or peripheral blood samples of newly diagnosed CBF-AML patients.Next Generation sequencing was used to detect 34 kinds of hematologic malignancy related gene mutations.2.Influencing factors of complete remission?CR₁?rate of one course of induction chemotherapy in patients with initial CBF-AML.Follow-up was conducted by consulting medical records and telephone follow-up.The time from diagnosis to death or the deadline of follow-up was overall survival?OS?,the first complete remission was CR₁,the first complete remission to the first recurrence or death was non-recurrence survival?RFS?,and the complete remission after one course of rescue chemotherapy was CR₂.Patients with CBF-AML were informed of their respective chemotherapy regimens by referring to the cases,and the differences in the chemotherapy regimens of CBF-AML patients between the groups were compared.The indicators and mutations of CR₁ group and non CR₁ group after one course of induction chemotherapy were compared and analyzed statistically.Combined with its clinical characteristics,the effect of related gene mutations on the complete remission rate?CR₁?of one course of induction chemotherapy was analyzed.Results:1.34 kinds of genes in bone marrow or peripheral blood of 43 patients were detected by Next Generation Sequencing?NGS?and the gene mutations were detected in16 out of 34.The mutation rate of KIT gene was the highest?48.8%?,followed by NRAS?16.3%?,ASXL1?16.3%?,TET2?11.6%?,CSF3R?9.3%?,FLT3?9.3%?,KRAS?7.0%?.The detection rates of mutations in different functional genes were as follows:genes related to signal transduction pathway?KIT,FLT3,CSF3R,KRAS,NRAS,JAK2,CALR,SH2B3,CBL?had the highest mutation frequency(72.1%?31/43?;epigenetic modification gene mutation frequency was 30.2%?13/43,including ASXL1,TET2,BCOR?;transcriptional regulation gene mutation frequency was 7.0%?3/43,including ETV6,UNX1,GATA2?.Splicing factor related gene mutation frequency was 2.3%?1/43,including ZRSR2?.2.The CR₁ rate was 74.4%after one course of induction chemotherapy.At first diagnosis,patients with low expression of WT1?the median value of WT1 was 788.9?were more likely to get CR₁?P=0.032?and the RFS of patients who got CR₁ after one course of induction chemotherapy was significantly longer than that of patients without CR₁[7.6?2.2-44.1?versus 5.8?1-19.4?,?P=0.048?].The rate of CR₁ in the signal transduction pathway gene mutation group was significantly lower than that in non-mutation group?64.5%vs 100%,P=0.045?,while the level of Serum hydroxybutyrate dehydrogenase?HBDH?was significantly higher than that in non-mutation group?418?154-2702?vs 246?110-1068?,P=0.032?.There was no difference in CD56 expression between the two groups?P=0.053?,which was limited to the difference between?>20%?expression and non-expression.?P=0.048?.Conclusion:In CBF-AML patients with mutations in signal transduction pathway genes,CR₁ is not easily obtained after one course of induction chemotherapy,and high levels of HBDH and CD56?>20%?expression are often associated with the onset of CBF-AML patients;compared with the patients who did not reach CR₁ in one course of treatment,the patients in CR₁ group often had lower WT1 expression and longer RFS.