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: DNA was extracted from bone marrow or peripheral blood samples of newly diagnosed CBF-AML patients admitted to the Hematology Department of the Second Hospital of Shanxi Medical University from January 2015 to January 2019. Next-generation sequencing was used for detection of 34 kinds of hematologic malignancy-related gene mutations in patients with CBF-AML, the effect of related gene mutations on the first complete remission (CR1) rate in one course of induction chemotherapy was analyzed by combineation with clinical characteristics.
Results: 34 kinds of genes in bone marrow or peripheral blood of 43 patients were detected by high throughput sequencing and the gene mutations were detected in 16 out of 34 genes. 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 with 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, RUNX1, GATA2). Splicing factor related gene mutation frequency was 2.3% (1/43), including ZRSR2). 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: CBF-AML patients with signal transduction pathway gene mutation are often accompanied by high HBDH level and CD56 expression, moreover, the remission rate induced by one course of treatment is low.
题目: 信号传导通路基因突变对CBF-AML患者一个疗程诱导缓解率的影响及临床特征分析.
目的: 研究融合基因外其他基因突变对核心结合因子相关急性髓系白血病（CBF-AML）患者1个疗程诱导化疗达首次完全缓解的影响.
方法: 采集2015年1月至2019年1月在山西医科大学第二医院血液科收治的43例初发CBF-AML患者的骨髓或外周血标本，提取DNA，通过高通量测序检测34种常见血液肿瘤基因突变情 况；结合其临床特征，分析相关基因突变对1个疗程诱导化疗完全缓解（CR1）率的影响.
结果: 43例初发CBF-AML患者初发时骨髓或外周血DNA均通过二代测序（NGS）检测了34种基因，其中16种基因存在突变，KIT基因突变率最高（48.8%），其次为NRAS（16.3%），ASXL1（16.3%），TET2（11.6%），CSF3R（9.3%），FLT3（9.3%）, KRAS（7.0%）。不同功能基因突变检出率依次为：信号传导通路基因（KIT、FLT3、CSF3R、KRAS、NRAS、JAK2、CALR、SH2B3、CBL）突变发生频率最高，为72.1%（31/43）；表观遗传修饰基因突变频率 为30.2%（13/43，包括ASXL1、TET2、BCOR）；转录调节基因突变频率为7.0%（3/43，包括ETV6、RUNX1、GATA2）；剪接因子相关基因为2.3%（1/43，包括ZRSR2）。经1个疗程诱导化疗CR1率为74.4%。初诊时WT1低表达（表达量临界值选取WT1中位值788.9）患者经1个疗程诱导化疗更易获得CR1（P=0.032），且1个疗程获CR1 组患者的RFS显著长于未获CR1组患者[7.6（2.2-44.1）对5.8（1-19.4），（P=0.048）]。信号传导通路基因突变组的1个疗程诱导治疗CR1率明显低于非信号传导通路基因突变组（64.5%对100%，P=0.045），但血清羟丁酸脱氢酶（HBDH）水平显著高于非突变组[418（154-2702）对246（110-1068），P=0.032]，2组CD56表达情况总体无差异（P=0.053），仅限于≥20%表达与不表达间存在差异（P=0.048）.
结论: 存在信号传导通路基因突变的CBF-AML患者常伴较高的HBDH水平和CD56表达，1疗程诱导缓解率低.