The Study On Expression Level Of Bcl2l12Gene In De Novo Acute Myeloid Leukemia And Its Clinical Significance

Objective Based on the detection of FLT3-ITD and NPM1gene mutations in de novo adultacute myeloid leukemia (AML) patients, to detect the BCL2L12gene expression levels in thesepatients. Exploring the relationship between FLT3-ITD, NPM1gene mutations and BCL2L12gene expression, and to discuss the relationship between BCL2L12gene expression and AMLpatients’ prognosis. Methods1. Bone marrows (BM) samples were collected from de novo adultAML patients and peripheral blood samples were collected from nomal control;2. Establishingstable and reliable RQ-PCR method to detect BCL2L12gene expression in AML patients;3.According to BCL2L12gene expressions, these AML patients were divided into some groupsanalyzing clinical features and prognosis. Results1. BCL2L12gene transcript level was detected in160AML patients and49healthy donors and BCL2L12gene expression levels in de novo AMLpatients (0.1238,0.0119-9.8725) were significant lower than those in healthy donors (0.2677,0.0173-1.2858, P<0.001). FLT3-ITD, NPM1gene mutations were tested in140AML pateints inwhich102cases harbored normal karyotype [29(20.7%) patients had NPM1+/FLT3-ITD-,9(6.4%) patients had NPM1+/FLT3-ITD+,14(10%) patients had NPM1-/FLT3-ITD+,88(62.9%)patients had NPM1-/FLT3-ITD-].2. The expression levels of BCL2L12were lower in NPM1-/FLT3-ITD+patients than in NPM1+/FLT3-ITD-ones both in AML patients and AML patientswith normal karyotype (median0.0886vs0.1774P=0.044and median0.1913vs0.2555P=0.045).3. AML patietns with lower BCL2L12expression had a higher FLT3-ITD mutation rate than thosewith higher BCL2L12gene expression (20.8%vs5%P=0.038).4. Relapsed or refractory AMLpatients harbored lower expression (median0.0915) compared with newly diagnosed patients(median0.1238P=0.036), and lower BCL2L12gene expression patients had a higher rate torelapse or be refractory (49.5%vs24%P=0.015).5. In patients with normal karyotype, the OS(median survival time24.8month vs9.17month P=0.016) and EFS (median survival time23.9month vs5.53month P=0.033) in patients with higher BCL2L12gene expression was significantlonger than lower expression group.6. In normal karyotype AML after age and white blood count(WBC) adjusted by Backward LR Cox mode, median OS and EFS of those patients with higherBCL2L12gene expression level were significantly longer than those with lower BCL2L12gene expression level (both P value were0.006). Conclusions1. De novo AML patients had relativelylower BCL2L12gene expression than normal controls.2. AML patients with lower BCL2L12gene expression had a higher FLT3-ITD mutation rate and most of them are relapsed or refractorypatients.3. In patients with normal karyotypes, the group with lower BCL2L12expression had ashorter OS and EFS than that with higher BCL2L12expression. Lower BCL2L12gene expressionis an independently adverse factor for the prognosis of AML patients with normal karyotypes.