The chromosomal translocation t(1;6)(p35.3;p25.2), recurrent in chronic lymphocytic leukaemia, leads to RCC1::IRF4 fusion

Sandrine Jayne; Cristina López; Natalie Put; Inga Nagel; Els Lierman; Eva Maria Murga Penas; Lucienne Michaux; Matthew J Ahearne; Harriet S Walter; Susanne Bens; Cosima Drewes; Monika Szczepanowski; Matthias Schlesner; Philip Rosenstiel; Iwona Wlodarska; Reiner Siebert; Martin J S Dyer

doi:10.1111/bjh.19790

The chromosomal translocation t(1;6)(p35.3;p25.2), recurrent in chronic lymphocytic leukaemia, leads to RCC1::IRF4 fusion

Br J Haematol. 2024 Dec;205(6):2321-2326. doi: 10.1111/bjh.19790. Epub 2024 Oct 15.

Authors

Sandrine Jayne¹, Cristina López^{2

3

4

5

6}, Natalie Put^{7

8

9

10}, Inga Nagel², Els Lierman⁷, Eva Maria Murga Penas², Lucienne Michaux⁷, Matthew J Ahearne¹, Harriet S Walter¹, Susanne Bens^{2

3}, Cosima Drewes³, Monika Szczepanowski^{11

12}, Matthias Schlesner^{13

14}, Philip Rosenstiel¹⁵, Iwona Wlodarska⁵, Reiner Siebert³, Martin J S Dyer¹

Affiliations

¹ The Ernest and Helen Scott Haematological Research Institute, Leicester Cancer Research Centre, University of Leicester, Leicester, UK.
² Institute of Human Genetics, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein-Campus Kiel, Kiel, Germany.
³ Institute of Human Genetics, Ulm University and Ulm University Medical Center, Ulm, Germany.
⁴ Institut D'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
⁵ Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
⁶ Universitat de Barcelona, Barcelona, Spain.
⁷ Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium.
⁸ Department of Oncology, Hematology and Radiotherapy, Ziekenhuis Oost-Limburg, Genk, Belgium.
⁹ Limburgs Oncologisch Centrum, Genk, Belgium.
¹⁰ Faculty of Medicine and Life Sciences, UHasselt-Hasselt University, Diepenbeek, Belgium.
¹¹ Hematopathology Section, Christian-Albrechts-University Kiel, Kiel, Germany.
¹² Second Medicine Department, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
¹³ Bioinformatics and Omics Data Analytics (B240), German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹⁴ Biomedical Informatics, Data Mining and Data Analytics, University of Augsburg, Augsburg, Germany.
¹⁵ Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany.

Abstract

The chromosomal translocation t(1;6)(p35.3;p25.2) is a rare but recurrent aberration in chronic lymphocytic leukaemia (CLL). We report molecular characterization of 10 cases and show that this translocation juxtaposes interferon regulatory factor 4 (IRF4) on 6p25 with regulator of chromosome condensation 1 (RCC1) on 1p35. The breakpoints fell within the 5' untranslated regions of both genes, resulting in RCC1::IRF4 fusion transcripts without alterations of the protein-coding sequences. Levels of expression of both RCC1 and IRF4 proteins were not obviously deregulated. The cases showed other mutations typical of CLL and we confirm previously reported skewing towards the IGHV-unmutated subtype. RCC1::IRF4 fusion characterizes a rare subset of CLL.

Keywords: CLL; IRF4; chromosomal translocation.

MeSH terms

Aged
Cell Cycle Proteins / genetics
Chromosomes, Human, Pair 1 / genetics
Chromosomes, Human, Pair 6* / genetics
Female
Guanine Nucleotide Exchange Factors / genetics
Humans
Interferon Regulatory Factors* / genetics
Leukemia, Lymphocytic, Chronic, B-Cell* / genetics
Male
Middle Aged
Nuclear Proteins / genetics
Oncogene Proteins, Fusion / genetics
Translocation, Genetic*

Substances

Interferon Regulatory Factors
interferon regulatory factor-4
Oncogene Proteins, Fusion
Nuclear Proteins
Guanine Nucleotide Exchange Factors
Cell Cycle Proteins

Abstract

MeSH terms

Substances

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