Transcriptomic and genomic heterogeneity in blastic plasmacytoid dendritic cell neoplasms: from ontogeny to oncogenesis.
Fiche publication
Date publication
mars 2021
Journal
Blood advances
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ADOTEVI Olivier, Pr DECONINCK Eric, Dr FERRAND Christophe, Pr GARNACHE-OTTOU Francine, Dr DAGUINDAU Etienne, Pr CALLANAN Mary, Dr ANGELOT-DELETTRE Fanny
Tous les auteurs :
Renosi F, Roggy A, Giguelay A, Soret L, Viailly PJ, Cheok M, Biichle S, Angelot-Delettre F, Asnafi V, Macintyre E, Geffroy S, Callanan M, Petrella T, Deconinck E, Daguindau E, Harrivel V, Bouyer S, Salaun V, Saussoy P, Feuillard J, Fuseau P, Saas P, Adotévi O, Jardin F, Ferrand C, Preudhomme C, Colinge J, Roumier C, Garnache-Ottou F
Lien Pubmed
Résumé
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.
Référence
Blood Adv. 2021 Mar 9;5(5):1540-1551