- Shang-Ju Wu1,
- Chien-Ting Lin1,*,
- Andreas Agathangelidis2,
- Liang-In Lin3,
- Yuan-Yeh Kuo4,
- Hwei-Fang Tien1 and
- Paolo Ghia5
- 1 Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taiwan;
- 2 Medicina Interna, Universita' Vita-Salute San Raffaele di Milano, Milano, Italy;
- 3 College of Medicine, National Taiwan University, Taiwan;
- 4 Graduate Institution of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan;
- 5 Universita' Vita-Salute San Raffaele and IRCCS Istituto Scientifico San Raffaele, Milano, Italy
- ↵* Corresponding author; email:
Differences in chronic lymphocytic leukemia between Asian and the Western population is widely known. To further clarify these ethnic differences, we profiled the molecular genetics in a cohort of 83 newly diagnosed patients from Taiwan. In detail, we assessed: (i) the usage and the mutational status of the clonotypic immunoglobulin heavy-chain variable region (IgHV) genes, (ii) the presence of VH CDR3 stereotypes and (iii) TP53, NOTCH1, SF3B1, BIRC3, and MYD88 mutations. The IgHV gene repertoire was biased and distinct from that observed in the West with the most common IgHV genes being IgHV3-23, IgHV3-7, and IgHV3-48. In terms of IgHV gene mutational status, 63.8% of patients carried mutated rearrangements, whereas 22.4% of patients were assigned to stereotyped subsets (6.9% to major subsets and 15.5%, minor ones). The frequencies of NOTCH1, SF3B1, BIRC3 and MYD88 mutations were 9.6%, 7.2%, 1.2%, and 2.4%, respectively; however, the frequency of TP53 mutation was significantly higher (20.5%). Patients with TP53 mutations or del(17p), SF3B1 mutations and unmutated IgHV had a worse outcome compared to the other patients. In conclusion, the differences observed in IgHV properties suggest different pathogenetic factors implicated in the development of chronic lymphocytic leukemia while the high TP53 mutation frequency could in part explain the dismal outcome of these patients in Taiwan.
- Received October 3, 2016.
- Accepted February 16, 2017.
- Copyright © 2017, Ferrata Storti Foundation