Mechanisms underlying the pathophysiology of primary Plasma Cell Leukemia (pPCL) and intramedullary multiple myeloma (MM) need to be further elucidated, being potentially relevant for improving therapeutic approaches. In such a context, the MM and pPCL subgroups characterized by t(11;14) deserve a focused investigation, as the presence of the translocation is mainly associated with sensitivity to venetoclax. Herein, we investigated a proprietary cohort of MM and pPCL patients, focusing on the transcriptional signature of samples carrying t(11;14), whose incidence increases in pPCL in association with an unfavorable outcome. In addition, we evaluated the expression levels of the BCL2-gene family members and of a panel of B-cell genes recently reported to be associated with sensitivity to venetoclax in MM. Moreover, transcriptional analysis of lncRNAs in the two clinical settings led to the identification of several differentially expressed transcripts, among which the SNGH6 deregulated lncRNA might be relevant in the pathogenesis and prognosis of pPCL with t(11;14). Overall, our data suggest that MMs and pPCLs with t(11;14) might be responsive to venetoclax based on different molecular programs, prompting further studies to elucidate better novel potential predictive biomarkers.

Transcriptomic analysis in multiple myeloma and primary plasma cell leukemia with t(11;14) reveals different expression patterns with biological implications in venetoclax sensitivity / K. Todoerti, E. Taiana, N. Puccio, V. Favasuli, M. Lionetti, I. Silvestris, M. Gentile, P. Musto, F. Morabito, U. Gianelli, N. Bolli, L. Baldini, A. Neri, D. Ronchetti. - In: CANCERS. - ISSN 2072-6694. - 13:19(2021), pp. 4898.1-4898.17. [10.3390/cancers13194898]

Transcriptomic analysis in multiple myeloma and primary plasma cell leukemia with t(11;14) reveals different expression patterns with biological implications in venetoclax sensitivity

Todoerti K.;Taiana E.;Favasuli V.;Lionetti M.;Silvestris I.;Gianelli U.;Bolli N.;Baldini L.;Neri A.;Ronchetti D.
2021

Abstract

Mechanisms underlying the pathophysiology of primary Plasma Cell Leukemia (pPCL) and intramedullary multiple myeloma (MM) need to be further elucidated, being potentially relevant for improving therapeutic approaches. In such a context, the MM and pPCL subgroups characterized by t(11;14) deserve a focused investigation, as the presence of the translocation is mainly associated with sensitivity to venetoclax. Herein, we investigated a proprietary cohort of MM and pPCL patients, focusing on the transcriptional signature of samples carrying t(11;14), whose incidence increases in pPCL in association with an unfavorable outcome. In addition, we evaluated the expression levels of the BCL2-gene family members and of a panel of B-cell genes recently reported to be associated with sensitivity to venetoclax in MM. Moreover, transcriptional analysis of lncRNAs in the two clinical settings led to the identification of several differentially expressed transcripts, among which the SNGH6 deregulated lncRNA might be relevant in the pathogenesis and prognosis of pPCL with t(11;14). Overall, our data suggest that MMs and pPCLs with t(11;14) might be responsive to venetoclax based on different molecular programs, prompting further studies to elucidate better novel potential predictive biomarkers.
LncRNA; Multiple myeloma; Plasma Cell Leukemia; SNHG6; T(11;14); Venetoclax
Settore MED/15 - Malattie del Sangue
H2020_ERC19NBOLL_01 - spontaneous Evolution and Clonal heterOgeneity in MoNoclonal Gammopathies: from mechanisms of progression to clinical management (bECOMiNG) - BOLLI, NICCOLO' - H2020_ERC - Horizon 2020_Europern Research Council - 2019
CANCERS
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/874133
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