Biological and clinical characteristics of patients with chronic lymphocytic leukemia with the IGHV3-21 and IGHV1-69; analysis of data from a single center

Abstract

This study aimed at mapping the frequency of IGHV3-21 and IGHV1-69 in a group of 417 patients newly diagnosed with chronic lymphocytic leukemia (CLL) and described basic characteristics, cytogenetic abnormalities and prognosis of these patient subgroups. IGHV3-21 was found in 29 patients (7%) and IGHV1-69 in 51 patients (12.4%). The median overall survival (OS) rates were 97 months and 85 months in the IGHV3-21 and IGHV1-69 groups, respectively. In this small group of patients, the study failed to show a difference in OS of IGHV3-21 patients with mutated and unmutated IGHV status (p<0.597). There was also no difference in OS between IGHV3-21 patients with mutated IGHV status and all patients in the group having unmutated IGHV status (p<0.245). On the other hand, patients with IGHV3-21 and the presence of some other adverse prognostic factors (age ≥ 65 years, lymphocyte count ≥ 50×109/L, serum thymidine kinase ≥ 9U/L, deletion of 17p) had statistically significantly worse OS than IGHV3-21 patients without the presence of these prognostic factors. The multivariate analysis of an entire group of Binet clinical stage A patients proved that the presence of IGHV3-21 is as an independent adverse prognostic factor even though there was no statistical difference in OS between patients with IGHV3-21 and those without IGHV3-21 in the entire group (p<0.769). Patients with IGHV1-69 had the same probablility of OS irrespective of the presence of other adverse prognostic factors; their OS was significantly shorter as compared with the other patients from the entire group (p<0.03).The study mapped the occurrence of recurrent cytogenetic changes detected by FISH in IGHV3-21 (subset #2 and non-subset #2) and IGHV1-69 and compared it with the occurrence of recurrent changes in the entire group of patients. In IGHV1-69 and in subset #2 IGHV3-21, higher proportions of deletion of 11q were found (30% and 31%, respectively), with the deletion being present in 19.2% of the entire group of patients. None of the 3 patients with IGHV3-21 and deletion of 17p had subset #2. Patients with subset #2 IGHV3-21 had higher proportions of deletion of 13 (69%) as compared with non-subset #2 IGHV3-21 patients (27%).

MYD88-Mutated Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma as a Distinctive Molecular Subgroup Is Associated with Atypical Immunophenotypes in Chinese Patients

“…Due to the fact that the presence of IGHV1-69 is associated with non-hypermutated IGHV status, IGHV1-69 is related to unfavourable prognosis. However, unlike IGHV3-21, which is identified as an independent predictor for prognosis in CLL/SLL, IGHV1-69 gene usage per se does not seem to be predictive of progressive disease, and progression is primarily related to the IGHV status [ 29 , 30 ]. In addition, IGHV1-69 has been reported to be closely linked to certain viruses and viral infections [ 31 ].…”

Association of Cytogenetics Aberrations and IGHV Mutations with Outcome in Chronic Lymphocytic Leukemia Patients in a Real-World Clinical Setting

“…In this family, we found a higher frequency of M-CLL cases, similar to previous reports. IGHV3-21 family has been associated with an unfavorable prognosis independently of the IGHV mutational status, [28][29][30][31][32] but we could not confirm this result due to the small number of this subgroup in our cohort. As a novel finding, we identified IGHV3-11 as a usage associated with dismal prognosis, with most of these patients belonging to the U-CLL subgroup and showing a shorter TTFT and OS than patients without this usage, is in line with previous work from our group.…”

“…The most frequent subfamily was IGHV3-23, most of them associated with M-CLL and showed a short TTFT than patients without this usage. Moreover, IGHV3-21 is more common in Northern and Central Europe and Scandinavian CLL population, [28][29][30] and it is more infrequent in Southern European countries, 16,20 probably due to this reason we had a low frequency in our study (2.6%). In this family, we found a higher frequency of M-CLL cases, similar to previous reports.…”