Evidence map›Paper›PMID 39711167›Full record

ArticleCancer medicine2024

Mutational Landscape of Bone Marrow CD19 and CD138 Cells in Waldenström Macroglobulinemia (WM) and IgM Monoclonal Gammopathy of Undetermined Significance (IgM MGUS).

Alessandra Trojani, Alessandro Beghini, Luca Emanuele Bossi, Marta Rachele Stefanucci, Cassandra Palumbo, Antonino Greco, Annamaria Frustaci, Barbara Di Camillo, Roberto Cairoli

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Article in Cancer medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Alessandra TrojaniNiguarda Hospital, Department of Hematology and Oncology, Milano, Italy.ORCID 0000-0002-7659-2968
Alessandro BeghiniDepartment of Health Sciences, University of Milano, Milano, Italy.ORCID 0000-0002-8234-3474
Luca Emanuele BossiNiguarda Hospital, Department of Hematology and Oncology, Milano, Italy.ORCID 0000-0001-6409-8391
Marta Rachele StefanucciNiguarda Hospital, Department of Hematology and Oncology, Milano, Italy.
Cassandra PalumboNiguarda Hospital, Department of Hematology and Oncology, Milano, Italy.
Antonino GrecoA.R.N.A.S. Ospedali Civico Di Cristina Benfratelli, Palermo, Italy.
Annamaria FrustaciNiguarda Hospital, Department of Hematology and Oncology, Milano, Italy.ORCID 0000-0003-2587-7901
Barbara Di CamilloDepartment of Information Engineering, University of Padova, Padova, Italy.
Roberto CairoliNiguarda Hospital, Department of Hematology and Oncology, Milano, Italy.ORCID 0000-0001-6372-2623

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDespite recurrent and activating mutations, including MYD88, CXCR4, ARID1A, KMT2D, and CD79B were identified, the genetic basis for Waldenström's Macroglobulinemia (WM) and the risk of progression of IgM MGUS to WM remain to be fully elucidated.

methodsWe investigated the mutation status of WM (n = 8), sWM (n = 7), and IgM MGUS (n = 5) patients, by performing high-throughput targeted AmpliSeq NGS on 117 target genes. Specifically, we analyzed the CD19+ cells from 15 WM/sWM patients and five IgM MGUS patients. We also analyzed the CD138+ cells from four WM/sWM patients and two IgM MGUS patients.

resultsWe detected the classic mutation MYD88L265P in 93% of WM/sWM and in 60% of IgM MGUS patients. The CXCR4S338Ter mutation was identified in 26% of WM/sWM patients, whereas it was undetectable in IgM MGUS subjects. Interestingly, we identified new mutated genes, including WNK2 somatic mutations affecting 46% of WM/sWM patients, for which a recurrent allelic variant (V1635Ter) was observed in this cohort. Moreover, sequencing evaluation revealed recurrently frameshift or missense mutations involving NFKB2 (L473Afs) in 60% of IgM MGUS and 20% of WM/sWM, PTPN13 (P1546Tfs) in 20% of IgM MGUS and 7% of WM/sWM, CARD11 (S622del) in 20% of IgM MGUS and 20% of WM/sWM, KMT2C (I823T) in all IgM MGUS and 93% of WM/sWM, and ATM in 20% of IgM MGUS and 47% of WM/sWM patients.

conclusionIn conclusion, we uncovered new insights into the mutational landscape of WM, depicting a more complex involvement of the NF-kB pathway, and providing evidence of the recurrence of some variants (MYD88, IL17RB, NFKB2, ATM, CARD11, PTPN13, and WNK2) also in IgM MGUS.

Indexed as

Antigens, CD19Immunoglobulin MMonoclonal Gammopathy of Undetermined SignificanceMutationSyndecan-1Waldenstrom MacroglobulinemiaAgedAged, 80 and overBone MarrowFemaleHigh-Throughput Nucleotide SequencingHumansMaleMiddle AgedMyeloid Differentiation Factor 88Receptors, CXCR4Antigens, CD19CD19 molecule, humanCXCR4 protein, humanImmunoglobulin MMyeloid Differentiation Factor 88Receptors, CXCR4SDC1 protein, humanSyndecan-1IgM monoclonal Gammopathy of undetermined significancemutationsNGSWaldenström Macroglobulinemia

Identifiers

PMID39711167
PMCPMC11664121

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.