The Expression And Significance Of ID1and CDX2Genes In Adult AML Patients

Objective Our study based on the detection of NPM1and FLT3-ITD gene mutations in adultacute myeloid leukemia (AML) patients, to establish ID1and CDX2gene expression testingsystem to observe the incidence of ID1and CDX2gene expression level in adult AML, to explorethe relationship between NPM1, FLT3-ITD gene mutations and ID1,CDX2gene expressions, todiscuss the correlation of ID1, CDX2gene expression and adult AML patients prognosis, and tryto use different gene expression and mutation characteristics to establish molecular screeningsystem for adult AML patients. Methods1. Bone marrow (BM) or peripheral blood specimenswere collected from adult AML patients;2. Stable and reiable PAGE method was used to detectNPM1,FLT3-ITD gene mutations and RQ-PCR method was used to detect ID1,CDX2geneexpressions in AML patiens;3. According to NPM1, FLT3-ITD gene mutations and ID1, CDX2gene expressions, AML patients were divided into some groups, the clinical features and prognosisof AML patients were analyzed by statistical software of SPSS-16. Results1. In all167de novoAML specimens, NPM1and FLT3-ITD gene mutations were tested in142pateints, ID1andCDX2gene expressions were detected in114examples.2. In the whole population (142patients)，117cases harbored normal karyotype[18(12.7%) patients had NPM1-/FLT3-ITD+,20(14.1%) patients had NPM1+/FLT3-ITD+,32(22.5%) patients had NPM1+/FLT3-ITD-,72(50.7%) patients had NPM1-/FLT3-ITD-].3. The relationship between ID1gene expression andAML：3.1ID1gene transcript levels were detectable in BM mononuclear cells from114AMLpatients[Median8525(range57~11233238)] and10healthy donors[Median280(range133-490)],and there was a statistically significant difference on expression level of ID1gene between theAML patients and normal donors（P<0.001）. The expression level of ID1gene was higher in thepoor prognosis group than the intermediate prognosis group [Poor (Median:36840, range：336~11233238); Intermediate (Median:6630, range:66~1840798)](P=0.006).3.2In the wholepopulation (114patients), the expression level of ID1gene was associated with older age (age≥60years VS <60years, P=0.002) and relatively WBC count (WBC≥10×109/L VS <10×109/L,P=0.005).3.3Young patients (age <60years), who were not obtained the complete remission (CR)after the first cycle of chemotherapy harbored the higher level of ID1gene than those who received CR (Median,7429VS1246, P=0.044).4. The relationship between CDX2gene expression andAML：4.1CDX2gene transcript levels were detected in bone marrow and peripheral bloodmononuclear cells from114AML[Median972(range14-867961)]patients and10healthydonors[Median90(range46-242)], there was a statistically significant difference on expressionlevel of CDX2gene between the AML patients and normal donor (P<0.001). CDX2gene higherexpression were observed in all14patients with FLT3-ITD gene mutation (P=0.013).4.2Minimalresidual disease (MRD) of CDX2gene expression were tested after chemotherapy in15patients,the expression of CDX2gene in11cases with CR were obviously decreased (range79~811423)during the follow-up. Conclusions According to the detection of NPM1, FLT3-ITD genemutations and ID1,CDX2gene expressions in more than100AML patients and analyzing theirclinical features and prognosis, we found that relatively higher expression levels of ID1gene wereseen mostly in AML patients with adverse cytogenetic characteristics and with relatively older age(age≥60years), and might be associated with poorer prognosis of AML. There might be is a closerelationship among CDX2abnormal gene expression, FLT3-ITD gene mutations and HOX genesfamily, and CDX2gene may become MRD testing index for AML patients. In summary, ID1andCDX2genes might be two adverse prognostic molecular markers for adult AML patients.