title: Prognostic significance of clonal diversity of immunoglobulin gene rearrangements in patients with diffuse large B-cell lymphoma.
abstract: Clonal diversity of the immunoglobulin (Ig) gene rearrangement represents the oligoclonality of B-cell neoplasm, and has been shown to be a marker for poor prognosis in acute lymphoblastic leukemia. However, no previous report has addressed its prognostic impact in diffuse large B-cell lymphoma (DLBCL). We investigated the clinical significance of clonal diversity in DLBCL patients. Lymph node samples from 98 DLBCL patients were examined for Ig heavy and light chain gene rearrangements using Southern blot analysis. Clonal diversity was defined as oligoclonality detected on Southern blotting as previously described, and PCR analysis for IgH oligoclonality was performed on parts of DLBCL samples with clonal diversity for confirming the Southern blot analysis results. We found that clonal diversity could be detected in 36 (36.7%) of DLBCL patients, and PCR analysis showed concordant results. Regarding the clinical relevance, clonal diversity was significantly associated with relapse or refractory disease. Survival analysis showed that clonal diversity is an independent prognostic factor in DLBCL (p=0.05, Cox's proportional hazard method), and stratified analyses found the most significant subgroup is the high-intermediate risk category (p=0.01, log-rank test). We conclude that clonal diversity of Ig gene rearrangements is associated with a high risk of relapse or refractory disease in DLBCL patients. It is also a factor of poor prognosis in DLBCL, especially for high-intermediate risk category.
authors.affiliation: Division of Medical Oncology, Department of Medicine, Taipei Veterans General Hospital, No. 201 Sec. 2 Shih-Pai Rd., Taipei 112, Taiwan.
authors.forename: Muh-Hwa
authors.initials: MH
authors.lastname: Yang
authors.forename: Chueh-Chuan
authors.initials: CC
authors.lastname: Yen
authors.forename: Shu-Chung
authors.initials: SC
authors.lastname: Chiang
authors.forename: Li-Yuan
authors.initials: LY
authors.lastname: Bai
authors.forename: Kuan-Der
authors.initials: KD
authors.lastname: Lee
authors.forename: Liang-Tsai
authors.initials: LT
authors.lastname: Hsiao
authors.forename: Ta-Chung
authors.initials: TC
authors.lastname: Chao
authors.forename: Wei-Shu
authors.initials: WS
authors.lastname: Wang
authors.forename: Jin-Hwang
authors.initials: JH
authors.lastname: Liu
authors.forename: Tzeon-Jye
authors.initials: TJ
authors.lastname: Chiou
authors.forename: Po-Min
authors.initials: PM
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015139:Blotting, Southern; D002648:Child; D005260:Female; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D012008:Recurrence; D016019:Survival Analysis