Genetic and Clinical Characteristics of Korean Chronic Lymphocytic Leukemia Patients with High Frequencies of MYD88 Mutations

Abstract

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries. However, CLL is relatively rare in Asia; its genetic features are rarely studied. Here, we aimed to genetically characterize Korean CLL patients and to elucidate the genetic and clinical associations based on data obtained from 113 patients at a single Korean institute. We used next-generation sequencing to explore the multi-gene mutational data and immunoglobulin heavy chain variable gene clonality with somatic hypermutation (SHM). MYD88 (28.3%), including L265P (11.5%) and V217F (13.3%), was the most frequently mutated gene, followed by KMT2D (6.2%), NOTCH1 (5.3%), SF3B1 (5.3%), and TP53 (4.4%). MYD88-mutated CLL was characterized by SHM and atypical immunophenotype with fewer cytogenetic abnormalities. The 5-year time to treatment (TTT) of the overall cohort was 49.8% ± 8.2% (mean ± standard deviation) and the 5-year overall survival was 86.2% ± 5.8%. Patients with SHM, isolated del(13q), TP53-wild type, and NOTCH1-wild type showed better results than those without these conditions. In the subgroup analyses, patients with SHM and L265P presented shorter TTT than patients with SHM but not L265P. In contrast, V217F was associated with a higher SHM percentage and showed a favorable prognosis. Our study revealed the distinct characteristics of Korean CLL patients with high frequencies of MYD88 mutations and their clinical relevance.

Molecular characteristics in Chinese with chronic lymphocytic leukemia by next‐generation sequencing: A single‐center retrospective analysis

“…To discuss the differences between NGS in CLL patients in China and other countries, we compare the data by NGS from our centre with the results from the Europe. 10 Interestingly, as shown in Figure 2C, MYD88 was the most frequently mutated gene in our centre, with a much higher incidence (20%) than in Europe (2.6%), as well as a higher incidence of TP53 (18.8% vs.10.2%), which were similar to those in Asian CLL patients, such as in Korean, 17 and other Chinese studies. 18,19 Greater exposure to hepatitis B-virus infection and other environmental factors might explain the increased frequency of MYD88 mutations in Chinese versus Western CLL.…”

“…18,20 NOTCH1 (14.1% vs. 17.0%), SF3B1 (5.9% vs. 14.1%) and ATM (7.1% vs. 11.7%), the most frequently mutated genes in Europe, were relatively uncommon in our centre, as well as in Asian countries such as Taiwan, China 21 and Korea. 17 In addition, IGLL5, which had a mutation frequency of 11.8% in our centre but was the most frequently mutated gene in a study from Wuhan, China (29.03%) 19 and was frequently mutated in Spanish CLL patients involved in IGH translocations (15.0%). 22 DNMT3A mutation was rare in CLL but had a mutation frequency of 8.2% in our centre.…”

“…Greater exposure to hepatitis B‐virus infection and other environmental factors might explain the increased frequency of MYD88 mutations in Chinese versus Western CLL 18,20 . NOTCH1 (14.1% vs. 17.0%), SF3B1 (5.9% vs. 14.1%) and ATM (7.1% vs. 11.7%), the most frequently mutated genes in Europe, were relatively uncommon in our centre, as well as in Asian countries such as Taiwan, China 21 and Korea 17 . In addition, IGLL5 , which had a mutation frequency of 11.8% in our centre but was the most frequently mutated gene in a study from Wuhan, China (29.03%) 19 and was frequently mutated in Spanish CLL patients involved in IGH translocations (15.0%) 22 .…”