Correlations Of Cytogenetic And Molecular Genetic Alterations With Prognosis In Acute Lymphoblastic Leukemia

The acute lymphoblastic leukemia is a kind of malignant clonal disease derived frombone marrow hematopoietic stem cells, which is significantly different from morphology,cytogenetics, immunochemistry, molecular genetics and clinical features. Recently, with thecontinuous development of cytogenetic and molecular biology techniques, people have muchmore thorough understanding of some abnormalities of cytogenetics and molecular geneticswhich are discovered and associated with the occurrence and prognosis of ALL as well.Purpose：Analyzing various abnormalities characteristic of cellular and moleculargenetics among ALL patients in our hospital. Acquiring the relationship between cytogenetics,molecular genetics and prognosis.Methods：Between January1,2008and December31,2012,202patients of de novo ALLwere enrolled in this study.116cases were male, and86cases were female. The median agewas17years (ranged from1year to83years). The samples were obtained from thepatients’bone marrow. After conventional culturing, chromosomes were analyzed byG-banding methods. The karyotypes were described according to 《Human CytogeneticsInternational Denomination System》(ISCN2005). Immunophenotypes were analyzed withdirect immunofluorescence and flow cytometry. Expression of fusion genes (BCR/ABL、TEL/AML1、E2A/PBX1) and genes rearrangement (IGH or TCRβ、TCRγ) were detectedusing reverse transcription-polymerase chain reaction (RT-PCR). Rearrangement of MLLgenes were detected by fluorescence in situ hybridization (FISH). ALL data were analyzedwith survival estimation methods and multivariate analysis.Results：1.The incidence of normal karyotypes was55.38%. Among the patients whohad abnormal karyotypes, there were30.12%cases with t(9;22),21.69%with hyperdiploid,15.66%with hypodiploid,15.66%with complex chromosome abnormalities,4.82%with t(1;19),3.61%with t(8;14) and2.41%with del（11q）. The incidence of some karyotypes(t(3;7)、t(4;11)、t(14;18)、t(17;19)、del(9q)) were rare, there was only one case respectively.The incidence of patients who had no molecular genetic alterations was57%. Among thepatients with molecular genetic alterations, there were46.51%cases with IGH or TCRβ、TCRγ,27.91%with BCR/ABL,9.3%with mixed types(two or more kinds of moleculargenetic alterations),5.81%with MLL,4.65%with TEL/AML1and3.49%with E2A/PBX1.While, the incidence of EVI1and E2A/HLF was rare, there was only one case respectively.2. The incidence of cytogenetic alternation in children group was29.5%and55.1%inadult group. While, there were5.1%pediatric cases with t(9;22), comparatively, that ratio was19.6%among adult patients（χ2=12.584, P=0.002）.3. For normal karyotypes, the3-year EFS rate and OS rate were41.4%and76.3%,respectively. Compared with this result, the prognosis of patients with hyperdiploid (3-yearEFS rate6.9%, OS rate47%) was poor, while, the prognosis of patients with t(9;22)(3-yearEFS rate8%, OS rate15%), hypodiploid (3-year EFS rate0, OS rate18.5%)and complexchromosome abnormalities (3-year EFS rate0, OS rate33.3%) were much worse(P <0.01).Multivariate analysis demonstrated that the prognosis relevance of t(9;22),complex and otherkaryotypes, and white cell count.4. For patients with no molecular genetic alterations, the3-year EFS rate and OS ratewere40.2%and60.8%, respectively. Compared with that, the prognosis of patients withBCR/ABL (3-year EFS rate9.5%, OS rate22.9%) were much worse(P <0.01).Conclusion：1.In our hospital, for abnormal karyotypes, the incidence of t(9;22)(q24;q11)is highest, hyperdiploid is following. For molecular genetic alterations, IGH or TCRβ、TCRγis the most common subtype, BCR/ABL is following.2. Compared with children group, the incidence of cytogenetic and molecular geneticalterations is much higher.3. The most favorable prognosis is normal karyotype, hyperdiploid is following. While,the prognosis of hypodiploid, t(9;22) and complex chromosome abnormalities are muchworse. 4. The prognosis which patients had no molecular genetic alterations is much better thanthat with BCR/ABL positive.