Polymorphism in IKZF1 gene affects clinical outcome in diffuse large B-cell lymphoma
IKZF1 encodes a transcription factor involved in B-cell maturation and differentiation. We genotyped 218 diffuse large B-cell lymphoma (DLBCL) patients and 715 unrelated controls using a TaqMan allelic discrimination assay. No statistical difference was observed in the genotype distribution of the IKZF1 rs4132601 polymorphism between DLBCL patients and controls. However, the 2-year PFS rate of patients with the IKZF1 TT genotype was 54.3% compared to 68.6% in those with the IKZF1 G+ genotypes. Moreover, the IKZF1 rs4132601 polymorphism retained its independent prognostic impact on PFS. A more pronounced effect of the IKZF1 TT genotype on PFS was detected in patients with low/intermediate low IPI-risk group. When analysis was restricted to patients with GCB-type pattern, those with the IKZF1 TT genotype achieved a lower 5-year OS rate than the patients with the IKZF1 G+ genotypes (19.6 vs. 56%). This study provides the first evidence for the association of IKZF1 variants with DLBCL outcome.
KeywordsIKZF1 Diffuse large B-cell lymphoma Gene polymorphism
MBi, AP, MBor, WM designed the experiments. MBi, AP performed the experiments. MBi, WM, ELM analyzed the data. MBoj, ELM collected the clinical data. MBi, MBr, MBoj collected patient material. DJK, EKW, MPS, TR, KW, ELM provided material. MBi, WM, ELM carried out figures/tables preparations. MBi wrote the manuscript. WM, ELM, AP carried out revision. All authors read and approved the final manuscript.
Compliance with ethical standards
Ethics approval and consent to participate
All experimental procedures were approved by the Bioethics Committee of Medical University of Lodz, Poland (RNN/141/13/KE).
Conflict of interest
The authors reported no potential conflicts of interests.
This work was supported by Grant from National Science Centre (project 2013/09/N/NZ5/00822) and by Medical University of Lodz grant (project 502-03/2-159-02/502-14-195).
- 11.Bartram T, Burkhardt B, Wössmann W, Seidemann K, Zimmermann M, Cario G, et al. Childhood acute lymphoblastic leukemia-associated risk loci IKZF1, ARID5B and CEBPE and risk of pediatric non-Hodgkin lymphoma: a report from the Berlin–Frankfurt–Münster Study Group. Leuk Lymphoma. 2014;13:1–3.Google Scholar
- 14.Yri OE, Ekstrøm PO, Hilden V, Gaudernack G, Liestøl K, Smeland EB, et al. Influence of polymorphisms in genes encoding immunoregulatory proteins and metabolizing enzymes on susceptibility and outcome in patients with diffuse large B-cell lymphoma treated with rituximab. Leuk Lymphoma. 2013;54:2205–14.CrossRefPubMedGoogle Scholar