Research Papers:

New generation sequencing of targeted genes in the classical and the variant form of hairy cell leukemia highlights mutations in epigenetic regulation genes

Elsa Maitre, Philippe Bertrand, Catherine Maingonnat, Pierre-Julien Viailly, Margaux Wiber, Dina Naguib, Véronique Salaün, Edouard Cornet, Gandhi Damaj, Brigitte Sola, Fabrice Jardin and Xavier Troussard _

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Oncotarget. 2018; 9:28866-28876. https://doi.org/10.18632/oncotarget.25601

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Elsa Maitre1, Philippe Bertrand2, Catherine Maingonnat2, Pierre-Julien Viailly2, Margaux Wiber3, Dina Naguib3, Véronique Salaün3, Edouard Cornet1,3, Gandhi Damaj1,5, Brigitte Sola1, Fabrice Jardin2,4 and Xavier Troussard1,3,5

1Normandie Univ, INSERM U1245, Université de Caen, Caen, France

2Normandie Univ, INSERM U1245, Université de Rouen, Rouen, France

3Laboratoire d’hématologie, CHU Caen, Caen, France

4Service d’hématologie, Centre Henri Becquerel, Rouen, France

5Institut d’Hématologie de Basse-Normandie, CHU Caen, Caen, France

Correspondence to:

Xavier Troussard, email: [email protected]

Keywords: hairy cell leukemia; next-generation sequencing; gene mutation; hairy cell leukemia variant; epigenetic regulation genes

Received: April 13, 2018     Accepted: May 24, 2018     Published: June 22, 2018


Classical hairy cell leukemia (HCL-c) is a rare lymphoid neoplasm. BRAFV600E mutation, detected in more than 80% of the cases, is described as a driver mutation, but additional genetic abnormalities appear to be necessary for the disease progression. For cases of HCL-c harboring a wild-type BRAF gene, the differential diagnosis of the variant form of HCL (HCL-v) or splenic diffuse red pulp lymphoma (SDRPL) is complex. We selected a panel of 21 relevant genes based on a literature review of whole exome sequencing studies (BRAF, MAP2K1, DUSP2, MAPK15, ARID1A, ARID1B, EZH2, KDM6A, CREBBP, TP53, CDKN1B, XPO1, KLF2, CXCR4, NOTH1, NOTCH2, MYD88, ANXA1, U2AF1, BCOR, and ABCA8). We analyzed 20 HCL-c and 4 HCL-v patients. The analysis of diagnostic samples mutations in BRAF (n = 18), KLF2 (n = 4), MAP2K1 (n = 3), KDM6A (n = 2), CDKN1B (n = 2), ARID1A (n = 2), CREBBP (n = 2) NOTCH1 (n = 1) and ARID1B (n = 1). BRAFV600E was found in 90% (18/20) of HCL-c patients. In HCL-c patients with BRAFV600E, other mutations were found in 33% (6/18) of cases. All 4 HCL-v patients had mutations in epigenetic regulatory genes: KDM6A (n = 2), CREBBP (n = 1) or ARID1A (n = 1). The analysis of sequential samples (at diagnosis and relapse) from 5 patients (2 HCL-c and 3 HCL-v), showed the presence of 2 new subclonal mutations (BCORE1430X and XPO1E571K) in one patient and variations of the mutated allele frequency in 2 other cases. In the HCL-v disease, we described new mutations targeting KDM6A that encode a lysine demethylase protein. This opens new perspectives for personalized medicine for this group of patients.

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