Melania Tesio: Laboratory of Onco-Hematology, Institut Necker Enfants Malades (INEM), Institut National de Recherche Médicale (INSERM) U1151, Paris, France
Natural killer/T-cell lymphoma (NKTCL) is a rare non-Hodgkin lymphoma strongly associated to Epstein-Barr virus infection. This malignancy, which originates from either NK or γδ T-cells, is clinically aggressive and challenging to diagnose owing, among other reasons, to its genetic and phenotypical heterogeneity.
By integrating genomic, transcriptomic and clinical data from 128 newly diagnosed samples, Jie Xiong and colleagues provided an impressive characterization of this disease (Figure). Based on genomic alterations, Epstein-Barr virus sequences and transcriptional profiles, the authors identified three distinct molecular subtypes in NKTCL: the TSIM subtype (mutations in JAK-STAT pathway and TP53), the MB subtype (MGA mutations and BRDT loss of heterozygosity) and the HEA subtype (HDAC9, EP300, and ARID1A mutations).
Remarkably, this molecular classification correlated with the cell of origin as well as with the clinical outcome following asparagine-based regiments. The MB and HEA subtypes, predominantly depicting a T-cell of origin, predicted the worst and the best prognoses, respectively. In contrast, the TSIM subtype, predominantly showing an NK-cell of origin, predicted an intermediate prognosis. Last, but not least, these three molecular subtypes showed sensitivity to distinct targeted drugs.
Hence, in addition to providing important criteria for risk-based stratification, the multiomics approach undertaken by Xiong et al may open the way to novel targeted therapies for a rare but aggressive disease.
Xiong J, Cui BW, Wang N, et al. Cancer Cell. 2020;37(3):403-419.e6.
Thanks to a multi-omic approach, Xiong et al identified three subtypes of NKTCL, which correlated to the cell of origin, clinical outcome and sensitivity to distinct targeted therapies.