PMID- 35454811
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 14
IP  - 8
DP  - 2022 Apr 10
TI  - Deciphering Genetic Alterations of Hairy Cell Leukemia and Hairy Cell 
      Leukemia-like Disorders in 98 Patients.
LID - 10.3390/cancers14081904 [doi]
LID - 1904
AB  - Hairy cell leukemia (cHCL) patients have, in most cases, a specific clinical and 
      biological presentation with splenomegaly, anemia, leukopenia, neutropenia, 
      monocytopenia and/or thrombocytopenia, identification of hairy cells that express 
      CD103, CD123, CD25, CD11c and identification of the V600E mutation in the B-Raf 
      proto-oncogene (BRAF) in 90% of cases. Monocytopenia is absent in vHCL and SDRPL 
      patients and the abnormal cells do not express CD25 or CD123 and do not present 
      the BRAF(V600E) mutation. Ten percent of cHCL patients are BRAF(WT) and the 
      distinction between cHCL and HCL-like disorders including the variant form of HCL 
      (vHCL) and splenic diffuse red pulp lymphoma (SDRPL) can be challenging. We 
      performed deep sequencing in a large cohort of 84 cHCL and 16 HCL-like disorders 
      to improve insights into the pathogenesis of the diseases. BRAF mutations were 
      detected in 76/82 patients of cHCL (93%) and additional mutations were identified 
      in Kruppel-like Factor 2 (KLF2) in 19 patients (23%) or CDKN1B in 6 patients 
      (7.5%). Some KLF2 genetic alterations were localized on the cytidine deaminase 
      (AID) consensus motif, suggesting AID-induced mutations. When analyzing 
      sequential samples, a clonal evolution was identified in half of the cHCL 
      patients (6/12 pts). Among the 16 patients with HCL-like disorders, we observed 
      an enrichment of MAP2K1 mutations in vHCL/SDRPL (3/5 pts) and genes involved in 
      the epigenetic regulation (KDM6A, EZH2, CREBBP, ARID1A) (3/5 pts). Furthermore, 
      MAP2K1 mutations were associated with a bad prognosis and a shorter time to next 
      treatment (TTNT) and progression-free survival (PFS), independently of the HCL 
      classification.
FAU - Maitre, Elsa
AU  - Maitre E
AUID- ORCID: 0000-0002-5967-8225
AD  - INSERM U1245, Normandie University, UNIROUEN, UNICAEN, 14032 Caen, France.
AD  - Laboratory of Hematology, University Hospital Caen, Avenue de la Cote de Nacre, 
      CEDEX, 14033 Caen, France.
AD  - Structure Federative SF-MOCAE, University Hospital Caen, Avenue de la Cote de 
      Nacre, CEDEX, 14033 Caen, France.
FAU - Tomowiak, Cecile
AU  - Tomowiak C
AUID- ORCID: 0000-0003-4093-6463
AD  - Department of Hematology, University Hospital Poitiers, 2 rue Miletrie, 86000 
      Poitiers, France.
FAU - Lebecque, Benjamin
AU  - Lebecque B
AUID- ORCID: 0000-0002-4890-336X
AD  - Laboratory Hematology, University Hospital Clermont-Ferrand, 58 rue Montalembert, 
      63000 Clermont-Ferrrand, France.
FAU - Bijou, Fontanet
AU  - Bijou F
AUID- ORCID: 0000-0001-6768-7175
AD  - Department of Hematology, Institut Bergonie, 229 Cours de l'Argonne, CEDEX, 33079 
      Bordeaux, France.
FAU - Benabed, Khaled
AU  - Benabed K
AD  - Department of Hematology, Centre Hospitalier Public du Cotentin, 46 rue du Val de 
      Saire, 50100 Cherbourg-en-Cotentin, France.
AD  - Department of Hematology, Centre Henri Becquerel, 1 rue d'Amiens, CEDEX, 76038 
      Rouen, France.
FAU - Naguib, Dina
AU  - Naguib D
AUID- ORCID: 0000-0002-8914-4814
AD  - Laboratory of Hematology, University Hospital Caen, Avenue de la Cote de Nacre, 
      CEDEX, 14033 Caen, France.
AD  - Structure Federative SF-MOCAE, University Hospital Caen, Avenue de la Cote de 
      Nacre, CEDEX, 14033 Caen, France.
FAU - Kerneves, Pauline
AU  - Kerneves P
AD  - Laboratory of Hematology, University Hospital Caen, Avenue de la Cote de Nacre, 
      CEDEX, 14033 Caen, France.
AD  - Structure Federative SF-MOCAE, University Hospital Caen, Avenue de la Cote de 
      Nacre, CEDEX, 14033 Caen, France.
FAU - Cornet, Edouard
AU  - Cornet E
AUID- ORCID: 0000-0003-1667-3421
AD  - INSERM U1245, Normandie University, UNIROUEN, UNICAEN, 14032 Caen, France.
AD  - Laboratory of Hematology, University Hospital Caen, Avenue de la Cote de Nacre, 
      CEDEX, 14033 Caen, France.
FAU - Viailly, Pierre-Julien
AU  - Viailly PJ
AUID- ORCID: 0000-0002-9636-8971
AD  - INSERM U1245, Normandie University, UNIROUEN, UNICAEN, 14032 Caen, France.
AD  - Department of Hematology, Centre Henri Becquerel, 1 rue d'Amiens, CEDEX, 76038 
      Rouen, France.
AD  - Hematology Institute, University Hospital Caen, Avenue de la Cote de Nacre, 14033 
      Caen, France.
FAU - Arsham, Jeffrey
AU  - Arsham J
AD  - Department of Hematology, University Hospital Poitiers, 2 rue Miletrie, 86000 
      Poitiers, France.
FAU - Sola, Brigitte
AU  - Sola B
AUID- ORCID: 0000-0001-7278-9651
AD  - INSERM U1245, Normandie University, UNIROUEN, UNICAEN, 14032 Caen, France.
FAU - Jardin, Fabrice
AU  - Jardin F
AD  - INSERM U1245, Normandie University, UNIROUEN, UNICAEN, 14032 Caen, France.
AD  - Department of Hematology, Centre Henri Becquerel, 1 rue d'Amiens, CEDEX, 76038 
      Rouen, France.
FAU - Troussard, Xavier
AU  - Troussard X
AD  - INSERM U1245, Normandie University, UNIROUEN, UNICAEN, 14032 Caen, France.
AD  - Laboratory of Hematology, University Hospital Caen, Avenue de la Cote de Nacre, 
      CEDEX, 14033 Caen, France.
AD  - Hematology Institute, University Hospital Caen, Avenue de la Cote de Nacre, 14033 
      Caen, France.
LA  - eng
GR  - ARPI2017/CHU CAEN/
PT  - Journal Article
DEP - 20220410
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC9028144
OTO - NOTNLM
OT  - BRAF
OT  - HCL
OT  - KLF2
OT  - MAP2K1
OT  - genetic alterations
OT  - hairy cell leukemia
OT  - hairy cell leukemia variant (vHCL)
OT  - hairy cell leukemia-like disorders
OT  - splenic diffuse red pulp lymphoma (SDRPL)
COIS- Xavier Troussard is a consultant for Innate Pharma, Astra Zeneca, Abbvie, the 
      other authors declare that there are no conflicts of interest.
EDAT- 2022/04/24 06:00
MHDA- 2022/04/24 06:01
PMCR- 2022/04/10
CRDT- 2022/04/23 01:05
PHST- 2022/02/28 00:00 [received]
PHST- 2022/04/05 00:00 [revised]
PHST- 2022/04/06 00:00 [accepted]
PHST- 2022/04/23 01:05 [entrez]
PHST- 2022/04/24 06:00 [pubmed]
PHST- 2022/04/24 06:01 [medline]
PHST- 2022/04/10 00:00 [pmc-release]
AID - cancers14081904 [pii]
AID - cancers-14-01904 [pii]
AID - 10.3390/cancers14081904 [doi]
PST - epublish
SO  - Cancers (Basel). 2022 Apr 10;14(8):1904. doi: 10.3390/cancers14081904.