Recurrent CDKN1B (p27) mutations in hairy cell leukemia

Sascha Dietrich, Jennifer Huellein, Stanley Chun-Wei Lee, Barbara Hutter, D. Gonzalez, Sandrine Jayne, Martin J.S. Dyer, Malgorzata Oles, Monica Else, Xiyang Liu, Mikolaj Slabicki, Bian Wu, Xavier Troussard, Jan Duerig, Mindaugas Andrulis, Claire Dearden, Christof von Kalle, Martin Granzow, Anna Jauch, Stefan FroehlingWolfgang Huber, Manja Meggendorfer, Torsten Haferlach, Anthony D. Ho, Daniela Richter, Benedikt Brors, Hanno Glimm, Estella Matutes, Omar Abdel Wahab, Thorsten Zenz

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)


Hairy cell leukemia (HCL) is marked by near 100% mutational frequency of BRAFV600E mutations. Recurrent cooperating genetic events that may contribute to HCL pathogenesis or affect the clinical course of HCL are currently not described. Therefore, we performed whole exome sequencing to explore the mutational landscape of purine analog refractory HCL. In addition to the disease-defining BRAFV600E mutations, we identified mutations in EZH2, ARID1A, and recurrent inactivating mutations of the cell cycle inhibitor CDKN1B (p27). Targeted deep sequencing of CDKN1B in a larger cohort of HCL patients identify deleterious CDKN1B mutations in 16% of patients with HCL (n = 13 of 81). In 11 of 13 patients the CDKN1B mutation was clonal, implying an early role of CDKN1B mutations in the pathogenesis of HCL. CDKN1B mutations were not found to impact clinical characteristics or outcome in this cohort. These data identify HCL as having the highest frequency of CDKN1B mutations among cancers and identify CDNK1B as the second most common mutated gene in HCL. Moreover, given the known function of CDNK1B, these data suggest a novel role for alterations in regulation of cell cycle and senescence in HCL with CDKN1B mutations.
Original languageEnglish
Pages (from-to)1005-1008
Number of pages4
Issue number8
Publication statusPublished - 20 Aug 2015

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