Title :

Transcriptomic and genomic heterogeneity in blastic plasmacytoid dendritic cell neoplasms: from ontogeny to oncogenesis

Author(s) :

Renosi, Florian [Auteur]
Roggy, Anne [Auteur]
Giguelay, Ambre [Auteur]
Soret, Lou [Auteur]
Viailly, Pierre-Julien [Auteur]
Cheok, Meyling [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Biichle, Sabeha [Auteur]
Angelot-Delettre, Fanny [Auteur]
Asnafi, Vahid [Auteur]
Macintyre, Elizabeth [Auteur]
Geffroy, Sandrine [Auteur]
Institut de Pathologie [CHU Lille]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Callanan, Mary [Auteur]
Petrella, Tony [Auteur]
Deconinck, Eric [Auteur]
Daguindau, Etienne [Auteur]
Harrivel, Véronique [Auteur]
Bouyer, Sabrina [Auteur]
Salaun, Véronique [Auteur]
Saussoy, Pascale [Auteur]
Feuillard, Jean [Auteur]
Fuseau, Pascal [Auteur]
Saas, Philippe [Auteur]
Adotévi, Olivier [Auteur]
Jardin, Fabrice [Auteur]
Ferrand, Christophe [Auteur]
Preudhomme, Claude [Auteur]
Institut de Pathologie [CHU Lille]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Colinge, Jacques [Auteur]
Institut régional de Cancérologie de Montpellier [ICM]
Institut de Recherche en Cancérologie de Montpellier [IRCM - U1194 Inserm - UM]
Université de Montpellier [UM]
Roumier, Christophe [Auteur]
Service de pathologie [CHU Lille]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Garnache-Ottou, Francine [Auteur]

Journal title :

Blood advances

Pages :

1540-1551

Publisher :

The American Society of Hematology

Publication date :

2021-03-09

ISSN :

2473-9529

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Abstract 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 ...
Show more >Abstract 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.Show less >

Language :

Anglais

Popular science :

Non

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277

Source :

Harvested from HAL