{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T21:36:32Z","timestamp":1778880992220,"version":"3.51.4"},"reference-count":26,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002456","name":"Chonnam National University","doi-asserted-by":"crossref","award":["2024-1954-01 to 04"],"award-info":[{"award-number":["2024-1954-01 to 04"]}],"id":[{"id":"10.13039\/501100002456","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Roche Pharmaceutical company","award":["ML40990"],"award-info":[{"award-number":["ML40990"]}]},{"name":"Korean Society of Hematology","award":["ICKSH-2025-06"],"award-info":[{"award-number":["ICKSH-2025-06"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic lymphocytic leukemia (CLL) is uncommon in Asia, and longitudinal genomic data from Asian cohorts are limited. We conducted serial whole-exome sequencing (WES) in a multicenter Korean cohort of newly diagnosed, elderly CLL treated with chlorambucil\u2013obinutuzumab to evaluate mutational heterogeneity and clonal hematopoiesis of indeterminate potential (CHIP) during treatment and follow-up. Tumor-only variants were filtered, restricted to nonsynonymous or loss-of-function coding\/splice-site mutations, and summarized as a binary patient-by-gene matrix for principal component analysis (PCA), trajectory analysis, and k-means clustering. CHIP was defined as \u22651 qualifying mutation in a prespecified CHIP gene set. Baseline PCA was more compact in patients with complete response at end of treatment, whereas partial response or progressive disease cases were more dispersed. PCA trajectories were compact and directionally consistent in complete responders, more dispersed in partial responders, and highly heterogeneous without a dominant direction in progressive disease. Clustering identified dispersed and compact clusters, and CHIP-associated mutations were enriched in the dispersed cluster (55.6% vs. 8.3%, Fisher\u2019s exact p = 0.0086). In paired samples collected 3\u20135 months after end of treatment, CHIP status changed in some patients. Serial WES may provide complementary information to treatment response, although these observations require confirmation in larger cohorts.<\/jats:p>","DOI":"10.3390\/ijms27062610","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T14:46:31Z","timestamp":1773326791000},"page":"2610","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Longitudinal Whole-Exome Sequencing Identifies Clonal Hematopoiesis and Genomic Heterogeneity as a Predictor of Treatment Outcome in Patients with Newly Diagnosed, Elderly Chronic Lymphocytic Leukemia"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1155-2298","authenticated-orcid":false,"given":"Ho Cheol","family":"Jang","sequence":"first","affiliation":[{"name":"Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun 58128, Jeollanam-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5203-2982","authenticated-orcid":false,"given":"Ga-Young","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun 58128, Jeollanam-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8519-4687","authenticated-orcid":false,"given":"Hyeonjin","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Nursing, Dongshin University, Naju 58245, Jeollanam-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ja Min","family":"Byun","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7833-8480","authenticated-orcid":false,"given":"Jee Hyun","family":"Kong","sequence":"additional","affiliation":[{"name":"Division of Hemato-Oncology, Wonju Severance Christian Hospital, Wonju 26426, Gangwon-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myung-won","family":"Lee","sequence":"additional","affiliation":[{"name":"Division to Hemato-Oncology, Chungnam National University Hospital, Daejeon 35015, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7956-468X","authenticated-orcid":false,"given":"Won Sik","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hematology, Inje University Busan Paik Hospital, Busan 47392, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2341-4911","authenticated-orcid":false,"given":"Ji Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Internal Medicine, Dong-A University College of Medicine, Busan 49236, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ho Sup","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kosin University College of Medicine, Kosin University Gospel Hospital, Busan 49267, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1252-5336","authenticated-orcid":false,"given":"Ho-Young","family":"Yhim","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju 54896, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deok-Hwan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun 58128, Jeollanam-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ahn, A., Kim, H.S., Kim, T.-Y., Lee, J.-M., Kang, D., Yu, H., Lee, C.Y., Kim, Y., Eom, K.-S., and Kim, M. 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