Challenging our understanding of B-cell lymphomagenesis and risk: Paediatric high-grade B-cell lymphoma, not otherwise specified with a DDX3X::MLLT10 fusion and an IGH deletion.
HGBL
MLLT10
NOS
lymphoma
Journal
Pediatric blood & cancer
ISSN: 1545-5017
Titre abrégé: Pediatr Blood Cancer
Pays: United States
ID NLM: 101186624
Informations de publication
Date de publication:
16 Dec 2023
16 Dec 2023
Historique:
revised:
26
11
2023
received:
12
08
2023
accepted:
28
11
2023
medline:
16
12
2023
pubmed:
16
12
2023
entrez:
16
12
2023
Statut:
aheadofprint
Résumé
We report a unique case of high-grade B-cell lymphoma, not otherwise specified in a 5-year-old child. Whole-genome sequencing revealed a DDX3X::MLLT10 fusion, usually seen in T-cell acute lymphoblastic leukaemia (ALL). This suggests the novel idea that MLLT10 fusions are capable of driving B-cell malignancies. An IGH deletion usually only seen in adults was also found. These unique genetic findings provide novel insights into B-cell lymphomagenesis. The child remains in remission 7 year post chemotherapy, which demonstrates that novel complex molecular findings do not always denote high-risk disease.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e30810Subventions
Organisme : Cancer Research UK Cambridge Centre clinical research fellowship
ID : C9685/A25117
Informations de copyright
© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.
Références
Uzunova L, Burke A. Update on non-Hodgkin lymphoma in children. Paediatrics and Child Health. 2016;26(2):57-62.
Alaggio R, Amador C, Anagnostopoulos I, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: lymphoid neoplasms. Leukemia. 2022;36(7):1720-1748.
Li J, Liu X, Yao Z, Zhang M. High-grade B-cell lymphomas, not otherwise specified: a study of 41 cases. Cancer Manag Res. 2020;12:1903-1912.
The National Genomics Research and Healthcare Knowledgebase v5. Genomics England; 2019. doi:10.6084/m9.figshare.4530893.v5
Tate JG, Bamford S, Jubb HC, et al. COSMIC: the catalogue of somatic mutations in cancer. Nucleic Acids Res. 2019;47(D1):D941-D947.
Brandimarte L, Pierini V, Di Giacomo D, et al. New MLLT10 gene recombinations in pediatric T-acute lymphoblastic leukemia. Blood. 2013;121(25):5064-5067.
Brandimarte L, La Starza R, Gianfelici V, et al. DDX3X-MLLT10 fusion in adults with NOTCH1 positive T-cell acute lymphoblastic leukemia. Haematologica. 2014;99(5):64-66.
Salmerón-Villalobos J, Ramis-Zaldivar JE, Balagué O, et al. Diverse mutations and structural variations contribute to Notch signaling deregulation in paediatric T-cell lymphoblastic lymphoma. Pediatr Blood Cancer. 2022;69(11):e29926.
Ries RE, Leonti AR, Triche TJ, et al. Structural variants involving MLLT10/AF10 are associated with adverse outcome in AML regardless of the partner gene-a COG/Tpaml study. Blood. 2019;134:461.
Deshpande AJ, Rouhi A, Lin Y, et al. The clathrin-binding domain of CALM and the OM-LZ domain of AF10 are sufficient to induce acute myeloid leukemia in mice. Leukemia. 2011;25(11):1718-1727.
Reindl L, Bacher U, Dicker F, et al. Biological and clinical characterization of recurrent 14q deletions in CLL and other mature B-cell neoplasms. Br J Haematol. 2010;151(1):25-36.
Tirado CA, Chen W, García R, Kohlman KA, Rao N. Genomic profiling using array comparative genomic hybridization define distinct subtypes of diffuse large B-cell lymphoma: a review of the literature. J Hematol Oncol. 2012;5:54.
Ortega-Molina A, Boss IW, Canela A, et al. The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development. Nat Med. 2015;21(10):1199-1208.
Jardin F, Jais J-P, Molina T-J, et al. Diffuse large B-cell lymphomas with CDKN2A deletion have a distinct gene expression signature and a poor prognosis under R-CHOP treatment: a GELA study. Blood. 2010;116(7):1092-1104.
Ramis-Zaldivar JE, Gonzalez-Farré B, Balagué O, et al. Distinct molecular profile of IRF4-rearranged large B-cell lymphoma. Blood. 2020;135(4):274-286.
Ferrero S, Rossi D, Rinaldi A, et al. KMT2D mutations and TP53 disruptions are poor prognostic biomarkers in mantle cell lymphoma receiving high-dose therapy: a FIL study. Haematologica. 2020;105(6):1604-1612.
Li JF, Dai YT, Lilljebjörn H, et al. Transcriptional landscape of B cell precursor acute lymphoblastic leukemia based on an international study of 1,223 cases. Proc Natl Acad Sci U S A. 2018;115(50):E11711-E11720.
Laharanne E, Chevret E, Idrissi Y, et al. CDKN2A-CDKN2B deletion defines an aggressive subset of cutaneous T-cell lymphoma. Mod Pathol. 2010;23(4):547-558.
Zhang W, Kuang P, Liu T. Prognostic significance of CDKN2A/B deletions in acute lymphoblastic leukaemia: a meta-analysis. Ann Med. 2019;51(1):28-40.
Olszewski A, Kurt H, Evens AM. Defining and treating high-grade B-cell lymphoma, NOS. Blood. 2022;140(9):943-954.
Gong C, Krupka JA, Gao J, et al. Sequential inverse dysregulation of the RNA helicases DDX3X and DDX3Y facilitates MYC-driven lymphomagenesis. Mol Cell. 2021;81(19):4059-4075.e11.
Burkhardt B, Michgehl U, Rohde J, et al. Clinical relevance of molecular characteristics in Burkitt lymphoma differs according to age. Nat Commun. 2022;13(1):3881.
Ojha J, Secreto CR, Rabe KG, et al. Identification of recurrent truncated DDX3X mutations in chronic lymphocytic leukaemia. Br J Haematol. 2015;169(3):445-448.
Juskevicius D, Lorber T, Gsponer J, et al. Distinct genetic evolution patterns of relapsing diffuse large B-cell lymphoma revealed by genome-wide copy number aberration and targeted sequencing analysis. Leukemia. 2016;30(12):2385-2395.
Alhejaily A, Day AG, Feilotter HE, Baetz T, Lebrun DP. Inactivation of the CDKN2A tumor-suppressor gene by deletion or methylation is common at diagnosis in follicular lymphoma and associated with poor clinical outcome. Clin Cancer Res. 2014;20(6):1676-1686.
Braun M, Pastorczak A, Fendler W, et al. Biallelic loss of CDKN2A is associated with poor response to treatment in pediatric acute lymphoblastic leukemia. Leuk Lymphoma. 2017;58(5):1162-1171.
Fagan RJ, Dingwall AK. COMPASS ascending: emerging clues regarding the roles of MLL3/KMT2C and MLL2/KMT2D proteins in cancer. Cancer Lett. 2019;458:56-65.
Heward J, Konali L, D'Avola A, et al. KDM5 inhibition offers a novel therapeutic strategy for the treatment of KMT2D mutant lymphomas. Blood. 2021;138(5):370-381.