BACKGROUND AND OBJECTIVES: Given the prognostic relevance that the identification of mutated and germline subgroups of chronic lymphocytic leukemia (CLL) has recently acquired we set out to analyze in depth individual VH gene usage rearrangements in patients with mutated and germline CLL. DESIGN AND METHODS: Using sequence analysis of FR1/JH polymerase chain reaction products, the VH immunoglobulin gene configuration was analyzed in 159 rearranged IgH alleles from 154 CLL patients. Having previously identified a spatial relationship between VH gene usage and JH proximity in patients with acute lymphocytic leukemia (ALL), we performed linear and Poisson regression analysis on patients with germline and mutated CLL against VH rearrangements from normal peripheral blood. RESULTS: Sequence analysis showed that 102 patients (64%) had mutated sequences (>2% DNA base pair changes) while 57 (36%) had germline sequences. The germline CLL group showed JH proximal overusage similar to that reported in ALL patients, while the mutated CLL group showed a pattern comparable to that of the control group (peripheral blood rearranged VH sequences). The CDR3 region was statistically longer in the patients with germline CLL than in those with mutated CLL. INTERPRETATION AND CONCLUSIONS: This study highlights differences in the VDJ profile in mutated and germline CLL, consistent with the suggestion that CLL comprises two subgroups. The interpretation of these differences is that the B-cell of CLL, particularly in the germline group, may derive from a pool that has been unable to follow or complete the normal pathway of B-cell differentiation.
BACKGROUND AND OBJECTIVES: Given the prognostic relevance that the identification of mutated and germline subgroups of chronic lymphocytic leukemia (CLL) has recently acquired we set out to analyze in depth individual VH gene usage rearrangements in patients with mutated and germline CLL. DESIGN AND METHODS: Using sequence analysis of FR1/JH polymerase chain reaction products, the VH immunoglobulin gene configuration was analyzed in 159 rearranged IgH alleles from 154 CLL patients. Having previously identified a spatial relationship between VH gene usage and JH proximity in patients with acute lymphocytic leukemia (ALL), we performed linear and Poisson regression analysis on patients with germline and mutated CLL against VH rearrangements from normal peripheral blood. RESULTS: Sequence analysis showed that 102 patients (64%) had mutated sequences (>2% DNA base pair changes) while 57 (36%) had germline sequences. The germline CLL group showed JH proximal overusage similar to that reported in ALL patients, while the mutated CLL group showed a pattern comparable to that of the control group (peripheral blood rearranged VH sequences). The CDR3 region was statistically longer in the patients with germline CLL than in those with mutated CLL. INTERPRETATION AND CONCLUSIONS: This study highlights differences in the VDJ profile in mutated and germline CLL, consistent with the suggestion that CLL comprises two subgroups. The interpretation of these differences is that the B-cell of CLL, particularly in the germline group, may derive from a pool that has been unable to follow or complete the normal pathway of B-cell differentiation.
Authors: Renee C Tschumper; Susan M Geyer; Megan E Campbell; Neil E Kay; Tait D Shanafelt; Clive S Zent; Grzegorz S Nowakowski; Timothy G Call; Gordon W Dewald; Diane F Jelinek Journal: J Clin Invest Date: 2008-01 Impact factor: 14.808
Authors: Zijun Y Xu-Monette; Jianyong Li; Yi Xia; Beryl Crossley; Robert D Bremel; Yi Miao; Min Xiao; Thomas Snyder; Ganiraju C Manyam; Xiaohong Tan; Hongwei Zhang; Carlo Visco; Alexandar Tzankov; Karen Dybkaer; Govind Bhagat; Wayne Tam; Hua You; Eric D Hsi; J Han van Krieken; Jooryung Huh; Maurilio Ponzoni; Andrés J M Ferreri; Michael B Møller; Miguel A Piris; Jane N Winter; Jeffrey T Medeiros; Bing Xu; Yong Li; Ilan Kirsch; Ken H Young Journal: J Immunother Cancer Date: 2019-10-22 Impact factor: 13.751
Authors: Alejandro Medina; Cristina Jiménez; M Eugenia Sarasquete; Marcos González; M Carmen Chillón; Ana Balanzategui; Isabel Prieto-Conde; María García-Álvarez; Noemí Puig; Verónica González-Calle; Miguel Alcoceba; Isabel Cuenca; Santiago Barrio; Fernando Escalante; Norma C Gutiérrez; Mercedes Gironella; Miguel T Hernández; Anna Sureda; Albert Oriol; Joan Bladé; Juan-José Lahuerta; Jesús F San Miguel; María-Victoria Mateos; Joaquín Martínez-López; María-José Calasanz; Ramón García-Sanz Journal: Blood Cancer J Date: 2020-02-06 Impact factor: 11.037
Authors: H Li; T Y Wang; Y Yin; P L Wang; Z Cheng; J P Li; W Li; F Y Zhu; C C Wu; Z M Luo; Y H Chen; H Xiao; S B Deng; Y Q Cao; G S Zhang; L G Qiu; H L Peng Journal: Zhonghua Xue Ye Xue Za Zhi Date: 2021-12-14