Immunoglobulin gene rearrangements in Chinese and Italian patients with chronic lymphocytic leukemia
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Marilisa Marinelli1,*, Caterina Ilari1,*, Yi Xia2,*, Ilaria Del Giudice1, Luciana Cafforio1, Irene Della Starza1, Sara Raponi1, Paola Mariglia1, Silvia Bonina1, Zhen Yu3, Wenjuan Yang3, Lugui Qiu3, Thomas Chan4, Alfonso Piciocchi5, Yok-Lam Kwong4, Eric Tse4, Jianyong Li2, Anna Guarini1, Wei Xu2, Robin Foà1
1Department of Cellular Biotechnologies and Hematology, “Sapienza” University, Rome, Italy
2Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
3Department of Lymphoma & Myeloma Institute of Hematology, CAMS & PUMC, Tianjin, China
4Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
5GIMEMA Data Center, GIMEMA Foundation, Rome, Italy
*These authors have contributed equally to this work
Robin Foà, e-mail: [email protected]
Keywords: chronic lymphocytic leukemia, IGHV, stereotyped receptors, Chinese CLL, Italian CLL
Received: December 22, 2015 Accepted: February 16, 2016 Published: March 01, 2016
Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the Western world, whereas in Asia the incidence is about 10 times lower. The basis for this ethnic and geographic variation is currently unknown. The aim of this study was to characterize IGHVDJ rearrangements and stereotype of the HCDR3 region in a series of 623 Chinese CLL, in order to identify possible differences in immunoglobulin gene usage and their potential pathogenetic implications. Chinese CLL were compared to 789 Italian CLL. Chinese patients showed a higher proportion of mutated IGHV and a more frequent usage of IGHV3-7, IGHV3-74, IGHV4-39 and IGHV4-59 genes. A significantly lower usage of IGHV1-69 and IGHV1-2 was documented, with comparable IGHV3-21 frequency (3% Chinese vs 3.8% Italian CLL). The proportion of known stereotyped receptors was significantly lower in Chinese (19.7%) than in Italian CLL (25.8%), despite a significantly higher frequency of subset #8 (p= 0.0001). Moreover, new paired clusters were identified among Chinese cases. Overall, these data support a potential different antigenic exposure between Eastern and Western CLL.
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