دورية أكاديمية
Transcriptomic and genomic heterogeneity in blastic plasmacytoid dendritic cell neoplasms: from ontogeny to oncogenesis.
| العنوان: | Transcriptomic and genomic heterogeneity in blastic plasmacytoid dendritic cell neoplasms: from ontogeny to oncogenesis. |
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| المؤلفون: | Renosi, Florian, Roggy, Anne, Giguelay, Ambre, Soret, Lou, Viailly, Pierre-Julien, Cheok, Meyling, Biichle, Sabeha, Angelot-Delettre, Fanny, Asnafi, Vahid, Macintyre, Elizabeth, Geffroy, Sandrine, Callanan, Mary, Petrella, Tony, Deconinck, Eric, Daguindau, Etienne, Harrivel, Véronique, Bouyer, Sabrina, Salaun, Véronique, Saussoy, Pascale, Feuillard, Jean, Fuseau, Pascal, Saas, Philippe, Adotévi, Olivier, Jardin, Fabrice, Ferrand, Christophe, Preudhomme, Claude, Colinge, Jacques, Roumier, Christophe, Garnache-Ottou, Francine |
| المساهمون: | UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service de biologie hématologique, UCL - (SLuc) Centre de theÌrapie tissulaire et cellulaire |
| المصدر: | Blood advances, Vol. 5, no. 5, p. 1540-1551 (2021) |
| بيانات النشر: | American Society of Hematology |
| سنة النشر: | 2021 |
| المجموعة: | DIAL@UCL (Université catholique de Louvain) |
| مصطلحات موضوعية: | Carcinogenesis, Dendritic Cells, Genomics, Humans, Lectins, C-Type, Membrane Glycoproteins, Myeloproliferative Disorders, Receptors, Immunologic, SOXC Transcription Factors, Transcriptome |
| الوصف: | Oncogenesis and ontogeny of blastic plasmacytoid dendritic cell neoplasm (BPDCN) remain uncertain, between canonical plasmacytoid dendritic cells (pDCs) and AXL+ SIGLEC6+ DCs (AS-DCs). We compared 12 BPDCN to 164 acute leukemia by Affymetrix HG-U133 Plus 2.0 arrays: BPDCN were closer to B-cell acute lymphoblastic leukemia (ALL), with enrichment in pDC, B-cell signatures, vesicular transport, deubiquitination pathways, and AS-DC signatures, but only in some cases. Importantly, 1 T-cell ALL clustered with BPDCN, with compatible morphology, immunophenotype (cCD3+ sCD3- CD123+ cTCL1+ CD304+), and genetics. Many oncogenetic pathways are deregulated in BPDCN compared with normal pDC, such as cell-cycle kinases, and importantly, the transcription factor SOX4, involved in B ontogeny, pDC ontogeny, and cancer cell invasion. High-throughput sequencing (HaloPlex) showed myeloid mutations (TET2, 62%; ASXL1, 46%; ZRSR2, 31%) associated with lymphoid mutations (IKZF1), whereas single-nucleotide polymorphism (SNP) array (Affymetrix SNP array 6.0) revealed frequent losses (mean: 9 per patient) involving key hematological oncogenes (RB1, IKZF1/2/3, ETV6, NR3C1, CDKN2A/B, TP53) and immune response genes (IFNGR, TGFB, CLEC4C, IFNA cluster). Various markers suggest an AS-DC origin, but not in all patients, and some of these abnormalities are related to the leukemogenesis process, such as the 9p deletion, leading to decreased expression of genes encoding type I interferons. In addition, the AS-DC profile is only found in a subgroup of patients. Overall, the cellular ontogenic origin of BPDCN remains to be characterized, and these results highlight the heterogeneity of BPDCN, with a risk of a diagnostic trap. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2473-9529 2473-9537 |
| العلاقة: | boreal:260869; http://hdl.handle.net/2078.1/260869Test; info:pmid/33687433; urn:ISSN:2473-9529; urn:EISSN:2473-9537 |
| DOI: | 10.1182/bloodadvances.2020003359 |
| الإتاحة: | https://doi.org/10.1182/bloodadvances.2020003359Test http://hdl.handle.net/2078.1/260869Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.65A55F39 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 24739529 24739537 |
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| DOI: | 10.1182/bloodadvances.2020003359 |