Study On The Molecular Markers Of IL7R And JAK3 In Adult Patients With Acute Lymphoblastic Leukemia

Part I Mutations and expression of IL7R gene and relevant clinical significance in adult acute Lymphocytic LeukemiaObjectives:Interleukin-7 receptor(IL-7R) is the receptor of Interleukin-7.IL-7R consists of IL-7Ra(coded by IL7R)and yc.This study was aimed to investigate the mutations and expression of IL7R gene in adult acute lymphoblastic leukemia(ALL).Methods:Exon 2-8 of IL7R were amplified,cloned and sequenced in adult ALL patients(144cases) to identify the frequency,position and types of IL7R mutation.Real-time quantitative polymerase chain reaction was used to detect IL7R mRNA espression of adult ALL patients.The co-existing of IL7R mutations and abnormal mRNA expression with NOTCH1 and PHF6 mutations were explored.Statistical analysis was carried out using the SPSS(Version 20.0).The differrences between groups in quantitative data such like white blood cell(WBC),bone marrow blasts and peripheral blood blasts were performed in nonparametric Mann-Whitney test.Comparisons of frequencies in qualitative data were made with Pearson’s chi-square test or Fishers exact test.Kaplan-Meier curves were used to assess survival.P values below 0.05 were considered statistically significant.Result:IL7R mutations were identified in 2.8% of adult T-ALL patients.All of them included deletion or insertion mutations in exon5 and exon6.This study observed five SNP(Single Nucleotide Polymorphisms)changed,located in exon2(rs1494558),exon4(rs1494555、rs2228141)and exon8(rs3194051、rs2229232); Furthermore, we found the co-existence of IL7R mutations with NOTCH1 mutations and/or PHF6 mutations in T-ALL.Compared with high IL7R expression group,patients with low IL7R expression possessed longer progression free survival time(PFS)(P=0.036).Conclusion:The patients with high expression of IL7R mRNA have shorter PFS, expression of IL7R in adult T-ALL may have a prognostic significance.Part II Mutations of JAK3 in adult T-cell acute Lymphocytic LeukemiaObjectives:JAK3 belongs to the Janus Kinase family,who plays an important role in the sinaling pathway cytokine-induced.Mutations of JAK3 has been documented in a significant portion of hematolocical malignancies.This study was aimed to investigate the mutations of JAK3 gene in adult T-cell acute lymphoblastic leukemia(T-ALL).Methods:Exon 6,11,12,15 and 19 of JAK3 were amplified and sequenced in adult ALL patients to identify the frequency,position,types and association with IL7R/JAK mutations of JAK3 mutation.Statistical analysis was carried out using the SPSS(Version 20.0).The differences between groups in quantitative data such like white blood cell(WBC),bone marrow blasts and peripheral blood blasts were performed in nonparametric Mann-Whitney test.Comparisons of frequencies in qualitative data were made with Pearson’s chi-square test or Fishers exact test.Kaplan-Meier curves were used to assess survival.P values below 0.05 were considered statistically significant.Result:JAK3 mutations were only identified in 12.8%(5/39) of adult T-ALL patients(39cases).A total of 3 types of points mutations(M511I, Y886end, R887H).Co-existing mutations with IL7R were identified in 1 case,while none with JAKl.In addition,the median age of IL7R/JAK mutations in T-ALL patients were older than the non mutations(38.4 vs. 27.9, P=0.017).The positive rate of CD8 in patients with IL7R/JAK was higher than the non mutations(27.3% vs.70.4%, P=0.019).Conclusion:IL7R/JAK mutation may involve in human T-cell leukemogenesis.