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The oncogenic partners in many of these cases remain unidentified. Therefore, we conducted a comprehensive analysis of 144 CLL samples with\n                    <jats:italic>IGH-<\/jats:italic>\n                    translocation excluding\n                    <jats:italic>IGH<\/jats:italic>\n                    ::\n                    <jats:italic>BCL2<\/jats:italic>\n                    ,\n                    <jats:italic>IGH<\/jats:italic>\n                    ::\n                    <jats:italic>CCND1<\/jats:italic>\n                    ,\n                    <jats:italic>IGH<\/jats:italic>\n                    ::\n                    <jats:italic>BCL3<\/jats:italic>\n                    and\n                    <jats:italic>IGH<\/jats:italic>\n                    ::\n                    <jats:italic>MYC<\/jats:italic>\n                    . By combining fluorescence in situ hybridization (FISH) with whole-genome, targeted sequencing, and RNA expression profiling, we identified 25\n                    <jats:italic>IG<\/jats:italic>\n                    -translocation partners; 12 were previously unreported. Of 142 cases, 107 (75%) displayed an unmutated\n                    <jats:italic>IGHV<\/jats:italic>\n                    . Genetic profiling showed a heterogenous distribution of chromosomal aberrations and recurrently mutated genes across the groups. Of 41 informative cases, 32 (78%) exhibited breakpoints driven by aberrant class-switch recombination (CSR), with prominent involvement of\n                    <jats:italic>IGHM<\/jats:italic>\n                    (9\/41) and\n                    <jats:italic>IGHG3<\/jats:italic>\n                    (9\/41). Three cases with unmutated\n                    <jats:italic>IGHV<\/jats:italic>\n                    carried a juxtaposition of the\n                    <jats:italic>IGH<\/jats:italic>\n                    locus 5\u2019 to the intact\n                    <jats:italic>NKX2.6<\/jats:italic>\n                    gene in chromosome 8p21.2 due to illegitimate VDJ recombination, associated with significant ectopic upregulation of\n                    <jats:italic>NKX2.6<\/jats:italic>\n                    transcriptional expression (FDR\u2009&lt;\u20090.001, logFC: 15). Similarly,\n                    <jats:italic>METRNL<\/jats:italic>\n                    , located at the telomere of chromosome 17q25, was identified as a translocation partner gene in four cases. Our findings expand the spectrum of the oncogenic translocation partners targeting\n                    <jats:italic>IGH<\/jats:italic>\n                    in CLL.\n                  <\/jats:p>","DOI":"10.1038\/s41375-026-02902-9","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T08:13:42Z","timestamp":1776932022000},"page":"1401-1410","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The spectrum of immunoglobulin heavy chain enhancer hijacking in chronic lymphocytic leukemia"],"prefix":"10.1038","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5160-4732","authenticated-orcid":false,"given":"Cosima","family":"Drewes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nnamdi","family":"Okeke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6188-1652","authenticated-orcid":false,"given":"Billy","family":"Jebaraj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4124-9837","authenticated-orcid":false,"given":"Christoph","family":"Wiegreffe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9764-4041","authenticated-orcid":false,"given":"Isabelle","family":"Kraus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sina","family":"Hillebrecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amani","family":"Awada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5263-495X","authenticated-orcid":false,"given":"Susanne","family":"Bens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9231-9291","authenticated-orcid":false,"given":"Emil","family":"Chteinberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Eichhorst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Datismann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5033-2236","authenticated-orcid":false,"given":"Martin J. 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