Hairy cell leukemia: a specific 17-gene expression signature points to new targets for therapy

Article Article scientifique Article Hairy cell leukemia: a specific 17-gene expression signature points to new targets for therapy eng 2022-04-27 2022-08 author Maitre Elsa 0000-0002-5967-8225 author Cornet Edouard author Debliquis Agathe author Drenou Bernard author Gravey François author Chollet Didier 27590 author Cheze Stephane author Docquier Mylene 513819 author Troussard Xavier author Matthes Thomas 0000-0002-4875-2477 27368 2013-2022 10.1007/s00432-022-04010-4 35476232 0171-5216 PMC9293816 Background: Hairy cell leukemia (HCL) is a rare chronic B cell malignancy, characterized by infiltration of bone marrow, blood and spleen by typical "hairy cells" that bear the BRAFV600E mutation. However, in addition to the intrinsic activation of the MAP kinase pathway as a consequence of the BRAFV600E mutation, the potential participation of other signaling pathways to the pathophysiology of the disease remains unclear as the precise origin of the malignant hairy B cells. Materials and methods: Using mRNA gene expression profiling based on the Nanostring technology and the analysis of 290 genes with crucial roles in B cell lymphomas, we defined a 17 gene expression signature specific for HCL. Results: Separate analysis of samples from classical and variant forms of hairy cell leukemia showed almost similar mRNA expression profiles apart from overexpression in vHCL of the immune checkpoints CD274 and PDCD1LG2 and underexpression of FAS. Our results point to a post-germinal memory B cell origin and in some samples to the activation of the non-canonical NF-κB pathway. Conclusions: This study provides a better understanding of the pathogenesis of HCL and describes new and potential targets for treatment approaches and guidance for studies in the molecular mechanisms of HCL. EBI3 Gene expression Hairy cell leukemia NF-KB pathway RGS13 B-Lymphocytes / pathology Humans Leukemia, Hairy Cell / drug therapy Leukemia, Hairy Cell / genetics Leukemia, Hairy Cell / metabolism Proto-Oncogene Proteins B-raf / genetics Proto-Oncogene Proteins B-raf / metabolism RNA, Messenger Transcriptome Dewey 616.07 Dewey 616 Dewey 590 137 Département de pathologie et immunologie 21F 56 Département de médecine 221 23 Institut de génétique et de génomique 0DH 44 Département de génétique et évolution 162 false 586 Analyses cellulaires et moléculaires des hémopathies malignes 929 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE161279 Journal of cancer research and clinical oncology 148 8 18fc2cbe-a17c-4292-9a43-5ae9f0f5cb56 Article (Published version) Public Article-scientifique-from-europePmc.pdf 823263 application/pdf CC BY-4.0 363aa5e1-24e4-4e47-b5b7-f7283ad17c53 Appendix Public 432_2022_4010_MOESM1_ESM.pdf 1183726 application/pdf 3ee442fd-181f-4630-b959-4f391642c57f Appendix Public 432_2022_4010_MOESM2_ESM.xlsx 11461 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 92634ebc-7dd8-4657-ba49-18cd1b5e8786 Appendix Public 432_2022_4010_MOESM3_ESM.xlsx 60215 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 1feae46a-a531-48b3-98a2-155e79353fb9 Appendix Public 432_2022_4010_MOESM4_ESM.xlsx 12248 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 618d364d-970c-4266-90fa-c1cff4b5ec36 Appendix Public 432_2022_4010_MOESM5_ESM.xlsx 15218 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 4ceb5f8f-bc76-491e-a9bd-ec4ba1a4023d Appendix Public 432_2022_4010_MOESM6_ESM.xlsx 17782 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet b0c1e3b1-0b1d-48c0-a4b4-bfab2d95df97 Appendix Public 432_2022_4010_MOESM7_ESM.docx 15250 application/vnd.openxmlformats-officedocument.wordprocessingml.document openAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine clinique / Département de médecine Centres et instituts / Institut de génétique et de génomique Faculté des sciences / Section de biologie / Département de génétique et évolution

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