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Here, we describe limited-cell FACS sequencing (LC-FACSeq), a reproducible, highly sensitive method of characterizing clonal evolution in rare cells relevant to different types of acute and chronic leukemias. We demonstrate the utility of LC-FACSeq for broad multigene gene panels and its application for monitoring sequential acquisition of mutations conferring therapy resistance and clonal evolution in long-term ibrutinib treatment of patients with chronic lymphocytic leukemia. This technique is generalizable for monitoring of other blood and marrow infiltrating cancers.<\/jats:p>","DOI":"10.1172\/jci.insight.134973","type":"journal-article","created":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T11:01:33Z","timestamp":1592391693000},"source":"Crossref","is-referenced-by-count":6,"title":["LC-FACSeq is a method for detecting rare clones in leukemia"],"prefix":"10.1172","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7720-3522","authenticated-orcid":true,"given":"Eileen Y.","family":"Hu","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine and Comprehensive Cancer Center,"},{"name":"Medical Scientist Training Program,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4275-5562","authenticated-orcid":true,"given":"James S.","family":"Blachly","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine and 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