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Here, we report the detailed clonality analysis in a patient with a diagnosis of B-cell acute lymphoblastic leukemia (B-ALL) followed by a histiocytic sarcoma (HS), in which we were able to study clonal evolution by applying next generation sequencing (NGS) to identify IG rearrangements and gene mutations. Using the sequence information of the NGS-based IG clonality analysis, multiple related subclones could be distinguished in the PAX5 P80R-mutated B-ALL. Notably, only one of these subclones evolved into HS after acquiring a <jats:italic>RAF1<\/jats:italic> mutation. This case demonstrates that NGS-based IG clonality assessment and mutation analysis provide clear added value for clonal comparison and thereby improves clinicobiological understanding.<\/jats:p>","DOI":"10.1007\/s00428-022-03428-y","type":"journal-article","created":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T16:13:17Z","timestamp":1665763997000},"page":"105-110","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["PAX5 P80R-mutated B-cell acute lymphoblastic leukemia with transformation to histiocytic sarcoma: clonal evolution assessment using NGS-based immunoglobulin clonality and mutation analysis"],"prefix":"10.1007","volume":"483","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2666-1742","authenticated-orcid":false,"given":"Leonie I.","family":"Kroeze","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Scheijen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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The samples originated from leftover patient materials obtained during routine care and were excluded from research regulations requiring informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"P.J.T.A.G. is the treasurer of the EuroClonality foundation. M.v.d.B. has received speaker\u2019s fees from Gilead. The other authors have no conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}