Spliceosome mutations are common in persons with myeloproliferative neoplasm-associated myelofibrosis with RBC-transfusion-dependence and correlate with response to pomalidomide

Chowdhury, Onima; O’Sullivan, Jennifer; Barkas, Nikolaos; Wang, Guanlin; Buck, Gemma; Hamblin, Angela; Tefferi, Ayalew; Al‐Ali, Haifa Kathrin; Barosi, Giovanni; Devos, Timothy; Gisslinger, Heinz; Jiang, Qian; Kiladjian, Jean‐Jacques; Mesa, Ruben A.; Passamonti, Francesco; Ribrag, Vincent; Schiller, Gary J.; Vannucchi, Alessandro M.; Zhou, Daobin; McMullin, Mary Frances; Zhong, Judy; Gale, Robert Peter; Mead, Adam J.; Catalano, John; Stevenson, William; Gastl, Günther; Linkesch, Werner; Droogenbroeck, Jan Van; Mineur, Philippe; Gupta, Vikas; Turner, Andrew R.; Nevill, Thomas J.; Li, Jianyong; Shen, Zhi-Xiang; Liu, Ting; Bordessoule, Dominique; Natarajan‐Amé, Shanti; Récher, Christian; Demory, Jean Loup; Schlenk, Richard F.; Grießhammer, Martin; Cazzola, Mario; Saglio, Giuseppe; Specchia, Giorgina; Rambaldi, Alessandro; Pane, Fabrizio; Zweegman, Sonja; Boekhorst, Peter te; Raymakers, Reinier; Km, Abdulkadyrov; Соколова, М А; Salogub, Galina; Zaritskiy, Andrey; Cervantes, Francisco; Hernández‐Boluda, Juan Carlos; Ojeda, Emilio; Tesfa, Daniel; Nilsson, Lars; Drummond, Mark W.; Reilly, John T.; Harrison, Claire; Milojković, Dragana; Rivera, Candido E.; Besa, Emmanuel C.; Deeg, H. Joachim; Mascarenhas, John; Prchal, Josef T.; Tiu, Ramón V.; Talpaz, Moshe; Wang, Jen C.; Rampal, Raajit K.; Rondelli, Damiano; McCaul, Kelly; Brown, Randall W.; Komatsu, Norio; Ohyashiki, Kazuma; Ando, Kiyoshi; Kawabata, Hiroshi; Takenaka, Katsuto; Hata, Tomoko; Vardiman, James W.

doi:10.1038/s41375-020-0979-6

“…The efficacy of IMiDs is well established in MM; although not included among standard therapeutic options, IMiDs were explored in MF setting about a decade ago: some retrospective studies in MF patients receiving these agents documented a higher response rate in the presence of mutations involving spliceosome SRSF2, U2AF1, ZRSR2 and SFRB1. 22,23 In this respect, a targeted high-throughput sequencing on PB of our patient, at the time of MF evolution, did not reveal any additional mutation. The IMiDs have demonstrated clinical activity in ameliorating anemia, thrombocytopenia and splenomegaly due to their anti-inflammatory, anti-proliferative and anti-angiogenic effects through inhibition of NF-kB mediated pro-inflammatory and apoptotic circulating cytokines, including IL-2R, IL-6, IL-10, IL-8, TGFβ and TNF-α, which are all significantly increased in MF patients.…”

Section: Discussionmentioning

confidence: 47%

“…The efficacy of IMiDs is well established in MM; although not included among standard therapeutic options, IMiDs were explored in MF setting about a decade ago: some retrospective studies in MF patients receiving these agents documented a higher response rate in the presence of mutations involving spliceosome SRSF2 , U2AF1 , ZRSR2 and SFRB1 22,23 . In this respect, a targeted high‐throughput sequencing on PB of our patient, at the time of MF evolution, did not reveal any additional mutation.…”

Section: Discussionmentioning

confidence: 65%

Lenalidomide: A double‐edged sword for concomitant multiple myeloma and post‐essential thrombocythemia myelofibrosis

Loscocco

¹

,

Antonioli

²

,

Romano

³

et al. 2021

Self Cite

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

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“…Heterozygous missense mutations around hotspot S34 and Q157 are described. 1–2 1–2 16 6 Associated with disease progression and reduced overall survival in MF [ 60 , 69 , 118 ] ZRSR2 Protein associates with the U2 auxiliary factor heterodimer, which is required for the recognition of a functional 3ʹ splice site in pre-mRNA splicing. Frameshift/nonsense and missense mutations are described.…”

Section: Mutational Landscape Of Mpnmentioning

confidence: 99%

<p>Impact of Mutational Profile on the Management of Myeloproliferative Neoplasms: A Short Review of the Emerging Data</p>

Loscocco

¹

,

Guglielmelli

²

,

Vannucchi

³

2020

OTT

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

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“…These mutations are mutually exclusive and do show correlation with disease phenotype and prognosis [5][6][7]. Additional mutations in genes involved in epigenetic regulation, affecting the RAS signaling pathway or the tumor suppressor TP53 also play a fundamental role in the transformation of the malignant cell and, therefore, in its clinical expression [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Clinical Characteristics and Outcomes of Patients with Primary and Secondary Myelofibrosis According to the Genomic Classification Using Targeted Next-Generation Sequencing

Garrote

¹

,

López‐Guerra

²

,

Arellano‐Rodrigo

³

et al. 2023

Cancers

Self Cite

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

Spliceosome mutations are common in persons with myeloproliferative neoplasm-associated myelofibrosis with RBC-transfusion-dependence and correlate with response to pomalidomide

Abstract: for the RESUME trialists (2020). Spliceosome mutations are common in persons with myeloproliferative neoplasm-associated myelofibrosis with RBC-transfusion-dependence and correlate with response to pomalidomide. Leukemia.

Cited by 9 publications

References 13 publications

Lenalidomide: A double‐edged sword for concomitant multiple myeloma and post‐essential thrombocythemia myelofibrosis

Lenalidomide: A double‐edged sword for concomitant multiple myeloma and post‐essential thrombocythemia myelofibrosis

<p>Impact of Mutational Profile on the Management of Myeloproliferative Neoplasms: A Short Review of the Emerging Data</p>

Clinical Characteristics and Outcomes of Patients with Primary and Secondary Myelofibrosis According to the Genomic Classification Using Targeted Next-Generation Sequencing

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