| Purposes:B-cell lymphoproliferative disorders (B-LPD) are a very heterogeneous group of tumors, whose differential diagnosis is frequently compromised by the lack of specific cytogenetic or molecular features. Our objective was to search for cytogenetic features that allow better to understand the pathogenesis and to different subtypes of B-LPD, and combined with clinical materials, to establish the prognostic role of cytogenetic aberrations in CLL and MCL.Methods:cytogenetic aberrations were carried out by fluorescence in situ hybridization (FISH) based on bone marrow or peripheral blood samples of total 331 cases with B-LPD diagnosed in our hospital. The DNA probes for FISH were include 3ql4(D13S25,Rbl),11q22-23(ATM),14q32(IGH translocation),17P13(p53),trisomy 12 (CSP12),6q23(MYB),8q24(c-MYC),1q21, t(11;14)(q 13;q32)(CCND1/IGH). Cytogenetic aberrations between subtypes of B-LPD were compared and its'prognostic role in CLL and MCL were carried out by SPSS software.Results:1.Cytogenetic aberrations in the different subtypes of B-LPDThe incidences of cytogenetic aberrations of each subtype of B-LPD were as follow: CLL(n=161):del(D13S25):48.8%,del(Rbl):27.3%, del(11q):13.1%,del(17p):12.5%,+12: 23.4%, t(IGH):17.4%, total positivity 79.5%. MCL(n=26):del(D13S25):52.0%, del(Rb1): 38.5%, del(11q):24.0%, del(17p):44.0%,+12:13.0%, t(IGH):92.0%, C-MYC aberration: 52.0%, total positivity:76.9%(except t(IGH)).SMZL(n=11):del(D13S25):18.2%, del(Rb1):16.7%, del(11q):0%,del(17p):0%,+12:27.3%,t(IGH):45.5%, total positivity: 81.8%; LPL/WM(n=34):del(D13S25):5.9%, del(Rb1):2.9%,del(11q):0%, del(17p): 11.8%,+12:6.5%, t(IGH):2.9%, del(6q):21.4%, total positivity:38.7%.HCL(n=13): del(D13S25):0%, del(Rb1):0%, del(11q):0%, del(17p):8.3%,+12:O%, t(IGH):23.1%, total positivity:27.3%. B-PLL(n=4):del(D13S25):50.0%, del(Rb1):50.0%, del (11q):0%,del(17p):75.0%,+12:0%,t(IGH):0%,total positivity:75.0%.MZL(n=5): del(D13S25):40%,del(Rb1):33.3%, del(11q):0%, del(17p):0%,+12:20%,t(IGH):20%, total positivity:80%.CD5+unclassified (n=18):del(D13S25):22.2%, del(Rb1):11.1%, del(11q):5.6%,del(17p):16.7%,+12:25.0%, t(IGH):33.3%,total positivity:64.7%. suspected SMZL(n=25):del(D13S25):16.0%, del(Rbl):8.0%, del(11q):0%,del(17p): 16.0%,+12:4.2%, t(IGH):16.0%, total positivity:41.7%.CD5-unclassified (n=12): del(D13S25):16.7%, del(Rbl):0%, del(11q):8.3%, del(17p):7.7%,+12:0%, t(IGH): 30.8%, total positivity:41.7%.The incidence of del(17p)in MCL is significantly higher than in CLL(p<0.001). The incidence of del(D13S25) is higher in CLL compared with SMZL(p=0.049).Compared with LPL/WM, CLL had significant higher rates of del(D13S25) (p<0.001),del(Rbl) (p=0.002),del(11q) (p=0.Q28), translocation of IGH (p=0.031)and total positivity(p< 0.001).IGH translocation was significantly higher in SMZL compared with LPL/WM (p=0.002). CD5+unclassified B-LPD had lower rate of del(D13S25) compared with CLL(p=0.045), and had lower rates of del(D13S25)(p=0.049),del(Rbl) (p=0.045)and del(17p)(p=0.031) compared with MCL. Taking patients with suspected SMZL and CD5-unclassified B-LPD as one group, the incidences of trisomy 12(2.8%vs.27.3%;p=0.035) and total positivity(41.7%vs.81.8%;p=0.036) is siginificantly lower than confirmed SMZL.2. The relationship between cytogenetic aberrations and the clinical characteristics and prognosis of B-LPD2.1 The relationship between cytogenetic aberrations and the clinical characteristics and prognosis of CLLDel(D13S25) and sole del(D13S25) primary occured in early clinical stage(Binet A stage or Rai 0 stage), while del(11q) primary occured in advanced clinical stages. In patients with CD38+,34.8%had del(11q), which was higher than in patients with CD38-(10.7%;p=0.003). The incidences of del(llq) and del(17p) is 28%and 32% respectively in patients with unmutated IGVH gene, which is significantly higher than 10.5%and 7.0%in patients with mutated IGVH gene(p=0.046 and p=0.003 respectively). While patients with mutated IGVH gene had higher rates of del(D13S25) (59.6 vs.36.0%;p=0.048) and sole del(D13S25) (35.1%vs.4.0%;p=0.003) than patients with unmutated IGVH.In the univariate analysis, del(11q) and del(17p) was the adverse prognositic facotors for time to first therapy(TTT), while sole del(D13S25) was the good prognositic facotor for TTT. Del(17p) was the the adverse prognositic facotors for overall survival(OS). Taking other clinical factors that might influence the survival togather, we construct Cox models for TTT and OS respectively. Only del(llq)(RR 2.68,p=0.001) and del(17p) (RR 2.13, p=0.013) were the independent adverse factors for TTT, while del(17p) (RR 3.31, p=0.016) and B symptoms (RR 2.32,p=0.029)were the independent adverse factors for OS.2.2 The relationship between cytogenetic aberrations and the clinical characteristics and prognosis of MCLDel(D13S25) was positively correlated with patients with MIPI medium or high risk group, age more than 60 years or elevated LDH. More than one additional cytogenetic aberrations occured primarily in patients withβ2-MG>6.0mg/1 or elevated LDH, and del(17p) also occured primarily in patients with elevated LDH.Del(17p),C-MYC aberration and more than one additional cytogenetic aberrations all influenced PFS and OS, while del(Rb1) influenced PFS and del(llq) influenced OS in the univariate analysis. In the multivariate analysis, del(17p) was the only adverse factor for PFS and OS.Conclusions:1. Del(D13S25) was a recurrent aberration in subtypes of B-LPD, indicating that these common aberrations target genes might have important role in B-cell lymphomagenesis.2. Cytogenetic aberrations might provide important clues for the differential diagnosis between subtypes of B-LPD, such as trisomy 12 for distinguishing SMZL from other CD5-cases, IGH translocation for distinguishing LPL/WM from other B-LPD and MM.3. In CLL, cytogenetic aberrations corrected with clinical stages, CD38 expression and IGVH mutational statue. Del(llq) and del(17p) were the independent factors for TTT, while del(17p) was the independent factor for OS in CLL4. Del(17p) was the only independent factor for OS in MCL.
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