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.

Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) includes heterogeneous conditions such as previous history and specific cytogenetic and morphological properties. In this study, we analyze genetic aberrations using an RNA-based next-generation sequencing (NGS) panel assay in 45 patients with AML-MRC and detect 4 gene fusions of KMT2A-SEPT9, KMT2A-ELL, NUP98-NSD1, and RUNX1-USP42 and 81 somatic mutations. Overall, all patients had genetic aberrations comprising of not only cytogenetic changes, but also gene fusions and mutations. We also demonstrated several characteristic genetic mutations according to the AML-MRC subgroup. TP53 was the most commonly mutated gene (n = 11, 24%) and all were found in the AML-MRC subgroup with myelodysplastic syndrome-defining cytogenetic abnormalities (AML-MRC-C) (p = 0.002). These patients showed extremely poor overall survival not only in AML-MRC, but also within the AML-MRC-C subgroup. The ASXL1 (n = 9, 20%) and SRSF2 (n = 7, 16%) mutations were associated with the AML-MRC subgroup with >50% dysplasia in at least two lineages (AML-MRC-M) and were frequently co-mutated (55%, 6/11, p < 0.001). Both mutations could be used as surrogate markers to diagnose AML-MRC, especially when the assessment of multilineage dysplasia was difficult. IDH1/IDH2 (n = 13, 29%) were most commonly mutated in AML-MRC, followed by CEBPA (n = 5, 11%), PTPN11 (n = 5, 11%), FLT3 (n = 4, 9%), IDH1 (n = 4, 9%), and RUNX1 (n = 4, 9%). These mutations were not limited in any AML-MRC subgroup and could have more significance as a risk factor or susceptibility marker for target therapy in not only AML-MRC, but also other AML categories.

Mikyoung Park, M.D., Ph.D., Jihyang Lim, M.D., Ph.D., Ari Ahn, M.D., Ph.D., Eun-Jee Oh, M.D., Ph.D., Jaewoo Song, M.D., Ph.D., Kyeong-Hee Kim, M.D., Ph.D., Jin-Yeong Han, M.D., Ph.D., Hyun-Woo Choi, M.D., Ph.D., Joo-Heon Park, M.D., Kyung-Hwa Shin, M.D., Ph.D., Hyerim Kim, M.D., Ph.D., Miyoung Kim, M.D., Ph.D., Sang-Hyun Hwang, M.D., Ph.D., Hyun-Young Kim, M.D., Ph.D., Duck Cho, M.D., Ph.D., and Eun-Suk Kang, M.D., Ph.D.. Ann Lab Med 2024;44:222-34. https://doi.org/10.3343/alm.2023.0298

Recently, the 5th edition of 'The World Health Organization (WHO) Classification of Tumors of Haematopoietic and Lymphoid Tissues' (WHO2022) was released in beta version [1]. In WHO2022, the classification of AML underwent changes, separating AML with defining genetic abnormalities from AML defined by differentiation (AML-Diff). Additionally, AML with myelodysplasia-related changes (AML-MRC) was renamed 'AML myelodysplasia-related' (AML-MR), with updates including the removal of morphology as a sole diagnostic premise, revised cytogenetic criteria, and a mutation-based definition. An independent proposal, the International Consensus Classification (ICC), was also published during the same period [2]. This study aims to compare and analyze these two classifications, focusing on AML's diagnostic criteria and entity definition.

Ari Ahn, M.D., Chan-Jeoung Park, M.D., Ph.D., Min-sun Kim, M.D., Young-Uk Cho, M.D., Ph.D., Seongsoo Jang, M.D., Ph.D., Mi Hyun Bae, M.D., Ph.D., Jung-Hee Lee, M.D., Ph.D., Je-Hwan Lee, M.D., Ph.D., Kyung-Nam Koh, M.D., Ph.D., and Ho Joon Im, M.D., Ph.D.. Ann Lab Med 2021;41:479-84. https://doi.org/10.3343/alm.2021.41.5.479

Ahn A, et al. Ann Lab Med. 2020 May;40(3):193-200. https://doi.org/10.3343/alm.2020.40.3.193