Response of high-risk MDS to azacitidine and lenalidomide is impacted by baseline and acquired mutations in a cluster of three inositide-specific genes

Leukemia
Matilde Y FolloL Cocco

Abstract

Specific myeloid-related and inositide-specific gene mutations can be linked to myelodysplastic syndromes (MDS) pathogenesis and therapy. Here, 44 higher-risk MDS patients were treated with azacitidine and lenalidomide and mutations analyses were performed at baseline and during the therapy. Results were then correlated to clinical outcome, overall survival (OS), leukemia-free-survival (LFS) and response to therapy. Collectively, 34/44 patients were considered evaluable for response, with an overall response rate of 76.25% (26/34 cases): 17 patients showed a durable response, 9 patients early lost response and 8 patients never responded. The most frequently mutated genes were ASXL1, TET2, RUNX1, and SRSF2. All patients early losing response, as well as cases never responding, acquired the same 3 point mutations during therapy, affecting respectively PIK3CD (D133E), AKT3 (D280G), and PLCG2 (Q548R) genes, that regulate cell proliferation and differentiation. Moreover, Kaplan-Meier analyses revealed that this mutated cluster was significantly associated with a shorter OS, LFS, and duration of response. All in all, a common mutated cluster affecting 3 inositide-specific genes is significantly associated with loss of response to aza...Continue Reading

References

Sep 20, 2002·Blood·James W VardimanRichard D Brunning
Apr 2, 2003·Nature Reviews. Immunology·Klaus Okkenhaug, Bart Vanhaesebroeck
Jun 26, 2003·Nucleic Acids Research·Pauline C Ng, Steven Henikoff
Mar 30, 2004·Biochemical Society Transactions·Z-Z YangB A Hemmings
Dec 31, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Matilde Y FolloLucio Cocco
Aug 14, 2009·Journal of Hematology & Oncology·Venumadhav KotlaAmit Verma
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Matilde Y FolloLucio Cocco
Jul 27, 2010·Journal of Cellular Physiology·Giulia RamazzottiLucio Cocco
Apr 27, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Martin JäderstenGhulam J Mufti
Apr 21, 2012·Briefings in Bioinformatics·Helga ThorvaldsdóttirJill P Mesirov
Jun 14, 2012·Leukemia & Lymphoma·Sergej KonoplevCarlos E Bueso-Ramos
Apr 19, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Carla FilìDomenico Russo
Sep 17, 2013·Journal of Cellular Biochemistry·Christiano Marcello Vaz BarbosaEdgar J Paredes-Gamero
Jul 20, 2014·Journal of Cell Science·Yong TangXiuchun Cindy Tian
Sep 19, 2014·Biochemical Society Transactions·Alessandro PoliMatilde Y Follo
Mar 31, 2015·Journal of Lipid Research·Lucio CoccoPann-Ghill Suh
Oct 7, 2015·Blood·Emma C Fink, Benjamin L Ebert
Nov 27, 2015·Expert Opinion on Therapeutic Targets·Sara MongiorgiMatilde Y Follo
Feb 27, 2016·Current Pharmaceutical Design·Sara MongiorgiLucio Cocco
Mar 11, 2016·Current Pharmaceutical Design·Carlo FinelliLucio Cocco
Aug 16, 2016·Clinical Lymphoma, Myeloma & Leukemia·Thomas Prebet, Amer Zeidan
Sep 19, 2016·Advances in Biological Regulation·Andrea Pellagatti, Jacqueline Boultwood
Jan 21, 2017·Journal of Cellular Biochemistry·Stefano RattiLucia Manzoli
Feb 9, 2017·Proceedings of the National Academy of Sciences of the United States of America·Gillian L DornanJohn E Burke
Mar 16, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·James A Kennedy, Benjamin L Ebert
Apr 22, 2017·Nature Communications·Pedro da Silva-CoelhoJoop H Jansen
May 28, 2017·Advances in Biological Regulation·Maria Rosaria RicciardiAgostino Tafuri
Oct 4, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Alessandro PoliMatilde Y Follo
Oct 8, 2017·Advances in Biological Regulation·Richard N ArmstrongAndrea Pellagatti
Nov 6, 2017·Advances in Biological Regulation·Stefano RattiMatilde Y Follo
May 26, 2018·Blood Cancer Journal·David P Steensma
Jun 6, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Qian-Yu LiHongmian Zhao

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Citations

Sep 23, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Alessandra CappelliniMatilde Y Follo
Apr 12, 2020·International Journal of Molecular Sciences·Eric Owusu ObengLucio Cocco
Oct 21, 2020·Journal of Clinical Laboratory Analysis·Yanli YangDianming Li
Jan 6, 2021·Proceedings of the National Academy of Sciences of the United States of America·Sung-Hyun KimJae-Yeol Joo
Sep 24, 2020·Progress in Lipid Research·Matilda Katan, Shamshad Cockcroft
Jun 11, 2021·Frontiers in Oncology·Stefano RattiRoberta Fiume
Jun 23, 2021·The Journal of Biological Chemistry·Jacob T JacksonSeth L Masters
Oct 6, 2021·Proceedings of the National Academy of Sciences of the United States of America·Hui JingBenjamin F Cravatt

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Methods Mentioned

BETA
MDS
ubiquitination

Software Mentioned

CLUSTER
Integrative Genomics Viewer
GraphPad Prism

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