The Study Of Immunologic, Cytogenetic, Clinical Prognostic Characteristics And Notch1 Mutation In T-cell Acute Lymphoblaslic Leukemia

Objective To explore the Immunologic,cytogenetic,clinical prognostic characteristics and Notch1 mutation in T-cell acute lymphoblaslic leukemia(T-ALL)。Methods①The data including morphology,immunology and cytogenetics of 148 patients with T-ALL newly diagnosed was analyzed retrospectively from 2000 to 2008, to study the immunologic and cytogenetic characteristics of T-ALL patients,and make prognostic analysis of 63 in-patients with intact clinical data,investigate the impact of myeloid antigen expression,CD34 expression and abnormal karotype on the Complete remission,(CR)rates and prognosis。②Using genomic PCR and direct sequencing technique to investigate the Notch1 mutation in T-ALL。Results①The T-lineage-associated antigen expressions were CD7＞CD2＞CD3＞CD5 successively.Among 148 cases of T-ALL,3(2.0%)was accompanied by B-lineage associated antigen CD19 and/or CD20 expression.Myeloid antigen expression was identified in 52 cases(35.1%),The expression of CD13 was higher than that of CD33,1 case of them expressed CD14 antigen.The positive rate of CD34 was43.2%,The positive rate of myeloid antigen expression in CD34~+-T-ALL(62.5 %)was significantly higher than that in CD34~--T-ALL(14.2%)(P＜0.01)。②124 patients had successful conventional cytogenetics(CC)studies and there were 74 (59.7%)eases with normal karyotype,50(40.3%)cases with abnormal karyotype。The detection rate and recurring rate of chromosome abnormalities both are low,10 recurring chromosomal abnormalities including:5q-,6q-,9p-,9q-,12p-,13q-,i(7q),t(10;11)(p13;q23),t(11;14)(pl3;q11)and t(9;22)(q34;q11)were detected。The frequencies of hypodiploid groups and hyperdiploid groups in this series both are low。The frequencies of more than 50 chromosomes groups in this series are lower than those in B-ALL。③In 63 in-patients,18 cases had myeloid antigens expression,whose CR rate was significantly lower than that of My~--T-ALL(47%vs 89%,p=0.001),but the median survivals between two groups showed no statistic significance(19 months vs 26 months,p＞0.05).The early CR rate and the median survival of CD34~+-T-ALL were significantly lower than that of CD34~--T-ALL(52.6%vs 88.8%,p=0.003;16 months vs 26 months,P＜0.05).55 patients had successful cytogenetic studies and there were 27 (49.1%)cases with abnormal karyotype.CR rate(58.3%vs 91.6%,p=0.008)and median survival(15 months vs 26 months,P＜0.05)of T-ALL with abnormal karyotype was significantly lower than that of T-ALL with normal karyotype.④In all 31 T-ALL, 12 patients(38.7%)had at least one Notch-1 mutation.In one case,Notch1 mutation at diagnosis was no longer detectable in remission,confirming that it was acquired leukemia-specific mutations other than germline polymorphisms.No mutations were found in B-ALL and other controls.Conclusion Immunophenotyping is an important tool for diagnosis of T-ALL. Immunophenotypic characteristics of T-ALL is heterogeneous.The types and frequencies of chromosomal abnormalities in T-ALL are clearly different from those in B-ALL supporting the notion that B-ALL and T-ALL are biologically distinct neoplasms.The high frequency of Notch1 mutation in T-ALL indicate that Notch1 mutation play a important role in T-ALL development.