Epigenetics in Myeloproliferative Neoplasms

被引：29

作者：

McPherson, Suzanne ^{[1
]}

McMullin, Mary Frances ^{[2
]}

Mills, Ken ^{[1
]}

机构：

[1] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Blood Canc Res Grp, Belfast, Antrim, North Ireland

[2] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Ctr Med Educ, Belfast, Antrim, North Ireland

来源：

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE | 2017年 / 21卷 / 09期

关键词：

myeloproliferative neoplasm; epigenetics; cell signalling; janus kinase; DNA methylation; histone modification; miRNA regulation; combination epigenetic therapy; TYROSINE KINASE JAK2; DISORDERS; MUTATION; MYELOFIBROSIS;

D O I：

10.1111/jcmm.13095

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

A decade on from the description of JAK2 V617F, the MPNs are circumscribed by an increasingly intricate landscape. There is now evidence that they are likely the result of combined genetic dysregulation, with several mutated genes involved in the regulation of epigenetic mechanisms. Epigenetic changes are not due to a change in the DNA sequence but are reversible modifications that dictate the way in which genes may be expressed (or silenced). Among the epigenetic mechanisms, DNA methylation is probably the best described. Currently known MPN-associated mutations now include JAK2, MPL, LNK, CBL, CALR, TET2, ASXL1, IDH1, IDH2, IKZF1 and EZH2. Enhancing our knowledge about the mutation profile of patients may allow them to be stratified into risk groups which would aid clinical decision making. Ongoing work will answer whether the use of epigenetic therapies as alterative pathway targets in combination with JAK inhibitors may be more effective than single agent treatment.

引用

页码：1660 / 1667

页数：8

共 62 条

[1] Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo [J].

Abdel-Wahab, Omar ;

Gao, Jie ;

Adli, Mazhar ;

Dey, Anwesha ;

Trimarchi, Thomas ;

Chung, Young Rock ;

Kuscu, Cem ;

Hricik, Todd ;

Ndiaye-Lobry, Delphine ;

LaFave, Lindsay M. ;

Koche, Richard ;

Shih, Alan H. ;

Guryanova, Olga A. ;

Kim, Eunhee ;

Li, Sheng ;

Pandey, Suveg ;

Shin, Joseph Y. ;

Telis, Leon ;

Liu, Jinfeng ;

Bhatt, Parva K. ;

Monette, Sebastien ;

Zhao, Xinyang ;

Mason, Christopher E. ;

Park, Christopher Y. ;

Bernstein, Bradley E. ;

Aifantis, Iannis ;

Levine, Ross L. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2013, 210 (12) :2641-2659

[2] Role of TET2 and ASXL1 Mutations in the Pathogenesis of Myeloproliferative Neoplasms [J].

Abdel-Wahab, Omar ;

Mu, Ayalew Tefferi ;

Levine, Ross L. .

HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA, 2012, 26 (05) :1053-+

[3] ASXL1 Mutations Promote Myeloid Transformation through Loss of PRC2-Mediated Gene Repression [J].

Abdel-Wahab, Omar ;

Adli, Mazhar ;

LaFave, Lindsay M. ;

Gao, Jie ;

Hricik, Todd ;

Shih, Alan H. ;

Pandey, Suveg ;

Patel, Jay P. ;

Chung, Young Rock ;

Koche, Richard ;

Perna, Fabiana ;

Zhao, Xinyang ;

Taylor, Jordan E. ;

Park, Christopher Y. ;

Carroll, Martin ;

Melnick, Ari ;

Nimer, Stephen D. ;

Jaffe, Jacob D. ;

Aifantis, Iannis ;

Bernstein, Bradley E. ;

Levine, Ross L. .

CANCER CELL, 2012, 22 (02) :180-193

[4] Activation of the thrombopoietin receptor by mutant calreticulin in CALR-mutant myeloproliferative neoplasms [J].

Araki, Marito ;

Yang, Yinjie ;

Masubuchi, Nami ;

Hironaka, Yumi ;

Takei, Hiraku ;

Morishita, Soji ;

Mizukami, Yoshihisa ;

Kan, Shin ;

Shirane, Shuichi ;

Edahiro, Yoko ;

Sunami, Yoshitaka ;

Ohsaka, Akimichi ;

Komatsu, Norio .

BLOOD, 2016, 127 (10) :1307-1316

[5] Survival and Disease Progression in Essential Thrombocythemia Are Significantly Influenced by Accurate Morphologic Diagnosis: An International Study [J].

Barbui, Tiziano ;

Thiele, Juergen ;

Passamonti, Francesco ;

Rumi, Elisa ;

Boveri, Emanuela ;

Ruggeri, Marco ;

Rodeghiero, Francesco ;

d'Amore, Emanuele S. G. ;

Randi, Maria Luigia ;

Bertozzi, Irene ;

Marino, Filippo ;

Vannucchi, Alessandro M. ;

Antonioli, Elisabetta ;

Carrai, Valentina ;

Gisslinger, Heinz ;

Buxhofer-Ausch, Veronika ;

Muellauer, Leonhard ;

Carobbio, Alessandra ;

Gianatti, Andrea ;

Gangat, Naseema ;

Hanson, Curtis A. ;

Tefferi, Ayalew .

JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (23) :3179-3184

[6] Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders [J].

Baxter, EJ ;

Scott, LM ;

Campbell, PJ ;

East, C ;

Fourouclas, N ;

Swanton, S ;

Vassiliou, GS ;

Bench, AJ ;

Boyd, EM ;

Curtin, N ;

Scott, MA ;

Erber, WN ;

Green, AR .

LANCET, 2005, 365 (9464) :1054-1061

[7] A decade of exploring the cancer epigenome - biological and translational implications [J].

Baylin, Stephen B. ;

Jones, Peter A. .

NATURE REVIEWS CANCER, 2011, 11 (10) :726-734

[8] Improved targeting of JAK2 leads to increased therapeutic efficacy in myeloproliferative neoplasms [J].

Bhagwat, Neha ;

Koppikar, Priya ;

Keller, Matthew ;

Marubayashi, Sachie ;

Shank, Kaitlyn ;

Rampal, Raajit ;

Qi, Jun ;

Kleppe, Maria ;

Patel, Hardik J. ;

Shah, Smit K. ;

Taldone, Tony ;

Bradner, James E. ;

Chiosis, Gabriela ;

Levine, Ross L. .

BLOOD, 2014, 123 (13) :2075-2083

[9] Mutation analysis of ASXL1, CBL, DNMT3A, IDH1, IDH2, JAK2, MPL, NF1, SF3B1, SUZ12, and TET2 in myeloproliferative neoplasms [J].

Brecqueville, Mandy ;

Rey, Jerome ;

Bertucci, Francois ;

Coppin, Emilie ;

Finetti, Pascal ;

Carbuccia, Nadine ;

Cervera, Nathalie ;

Gelsi-Boyer, Veronique ;

Arnoulet, Christine ;

Gisserot, Olivier ;

Verrot, Denis ;

Slama, Borhane ;

Vey, Norbert ;

Mozziconacci, Marie-Joelle ;

Birnbaum, Daniel ;

Murati, Anne .

GENES CHROMOSOMES & CANCER, 2012, 51 (08) :743-755

[10] Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis [J].

Cervantes, Francisco ;

Vannucchi, Alessandro M. ;

Kiladjian, Jean-Jacques ;

Al-Ali, Haifa Kathrin ;

Sirulnik, Andres ;

Stalbovskaya, Viktoriya ;

McQuitty, Mari ;

Hunter, Deborah S. ;

Levy, Richard S. ;

Passamonti, Francesco ;

Barbui, Tiziano ;

Barosi, Giovanni ;

Harrison, Claire N. ;

Knoops, Laurent ;

Gisslinger, Heinz .

BLOOD, 2013, 122 (25) :4047-4053

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