The Clinical, Molecular, and Mechanistic Basis of RUNX1 Mutations Identified in Hematological Malignancies

被引:18
作者
Yokota, Asumi [1 ,2 ]
Huo, Li [1 ,2 ,3 ]
Lan, Fengli [1 ,2 ,4 ]
Wu, Jianqiang [1 ,2 ]
Huang, Gang [1 ,2 ]
机构
[1] Cincinnati Childrens Hosp Med Ctr, Div Pathol, Cincinnati, OH 45229 USA
[2] Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA
[3] Soochow Univ, Jiangsu Inst Hematol, Key Lab Thrombosis & Hemostasis, Minist Hlth,Affiliated Hosp 1, Suzhou 215006, Peoples R China
[4] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Pediat, Wuhan 430022, Peoples R China
关键词
clinical incidence and prognosis; pathogenesis; RUNX1; mutations; targeted therapy; ACUTE MYELOID-LEUKEMIA; FAMILIAL PLATELET DISORDER; CHRONIC MYELOMONOCYTIC LEUKEMIA; POINT MUTATIONS; MYELODYSPLASTIC SYNDROME; SOMATIC MUTATIONS; AML1/PEBP2-ALPHA-B GENE; HEMATOPOIETIC STEM; PROGNOSTIC MODEL; CLONAL EVOLUTION;
D O I
10.14348/molcells.2019.0252
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
RUNX1 plays an important role in the regulation of normal hematopoiesis. RUNX1 mutations are frequently found and have been intensively studied in hematological malignancies. Germline mutations in RUNX1 cause familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML). Somatic mutations of RUNX1 are observed in various types of hematological malignancies, such as AML, acute lymphoblastic leukemia (ALL), myelodysplastic syndromes (MDS), myeloproliferative neoplasm (MPN), chronic myelomonocytic leukemia (CMML), and congenital bone marrow failure (CBMF). Here, we systematically review the clinical and molecular characteristics of RUNX1 mutations, the mechanisms of pathogenesis caused by RUNX1 mutations, and potential therapeutic strategies to target RUNX1-mutated cases of hematological malignancies.
引用
收藏
页码:145 / 152
页数:8
相关论文
共 50 条
  • [41] RUNX1 mutations in cytogenetically normal acute myeloid leukemia are associated with a poor prognosis and up-regulation of lymphoid genes
    Greif, Philipp A.
    Konstandin, Nikola P.
    Metzeler, Klaus H.
    Herold, Tobias
    Pasalic, Zlatana
    Ksienzyk, Bianka
    Dufour, Annika
    Schneider, Friederike
    Schneider, Stephanie
    Kakadia, Purvi M.
    Braess, Jan
    Sauerland, Maria Cristina
    Berdel, Wolfgang E.
    Buechner, Thomas
    Woermann, Bernhard J.
    Hiddemann, Wolfgang
    Spiekermann, Karsten
    Bohlander, Stefan K.
    HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2012, 97 (12): : 1909 - 1915
  • [42] A novel RUNX1 mutation in familial platelet disorder with propensity to develop myeloid malignancies
    Kirito, Keita
    Sakoe, Kumi
    Shinoda, Daisuke
    Takiyama, Yoshihisa
    Kaushansky, Kenneth
    Komatsu, Norio
    HAEMATOLOGICA, 2007, 93 (01) : 155 - 156
  • [43] The ability of MLLto bind RUNX1 and methylate H3K4 at PU. 1 regulatory regions is impaired by MDS/AML-associated RUNX1/AML1 mutations
    Huang, Gang
    Zhao, Xinghui
    Wang, Lan
    Elf, Shannon
    Xu, Hao
    Zhao, Xinyang
    Sashida, Goro
    Zhang, Yue
    Liu, Yan
    Lee, Jennifer
    Menendez, Silvia
    Yang, Youyang
    Yan, Xiaomei
    Zhang, Pu
    Tenen, Daniel G.
    Osato, Motomi
    Hsieh, James J. -D.
    Nimer, Stephen D.
    BLOOD, 2011, 118 (25) : 6544 - 6552
  • [44] AML with RUNX1::RUNX1T1 Cooperating two Mutations Relapsed Quickly after Achieving CR
    Yang, Xinhong
    Wu, Yingwei
    Yang, Xiaofeng
    Wu, Xue
    Chen, Yingying
    Zhang, Rongjuan
    Zhang, Zhihua
    CLINICAL LABORATORY, 2024, 70 (03) : 619 - 621
  • [45] Prognostic effect of RUNX1 mutations in myelodysplastic syndromes: a meta-analysis
    He, Wei
    Zhao, Caifang
    Hu, Huixian
    HEMATOLOGY, 2020, 25 (01) : 494 - 501
  • [46] Thrombocytopenia and Predisposition to Acute Myeloid Leukemia due to Mosaic Ring 21 with Loss of RUNX1: Cytogenetic and Molecular Characterization
    Vormittag-Nocito, Erica
    Ni, Hongyu
    Schmidt, Mary L.
    Lindgren, Valerie
    MOLECULAR SYNDROMOLOGY, 2018, 9 (06) : 306 - 311
  • [47] Spectrum of abnormalities and clonal transformation in germline RUNX1 familial platelet disorder and a genomic comparative analysis with somatic RUNX1 mutations in MDS/MPN overlap neoplasms
    DiFilippo, Emma C.
    Coltro, Giacomo
    Carr, Ryan M.
    Mangaonkar, Abhishek A.
    Binder, Moritz
    Khan, Shakila P.
    Rodriguez, Vilmarie
    Gangat, Naseema
    Wolanskyj, Alexandra
    Pruthi, Rajiv K.
    Chen, Dong
    He, Rong
    Viswanatha, David S.
    Lasho, Terra
    Finke, Christy
    Tefferi, Ayalew
    Pardanani, Animesh
    Patnaik, Mrinal M.
    LEUKEMIA, 2020, 34 (09) : 2519 - 2524
  • [48] C-terminal RUNX1 mutation in familial platelet disorder with predisposition to myeloid malignancies
    Kozubik, Katerina Stano
    Radova, Lenka
    Pesova, Michaela
    Reblova, Kamila
    Trizuljak, Jakub
    Plevova, Karla
    Fiamoli, Veronika
    Gumulec, Jaromir
    Urbankova, Helena
    Szotkowski, Tomas
    Mayer, Jiri
    Pospisilova, Sarka
    Doubek, Michael
    INTERNATIONAL JOURNAL OF HEMATOLOGY, 2018, 108 (06) : 652 - 657
  • [49] RUNX1 mutations mitigate quiescence to promote transformation of hematopoietic progenitors in Fanconi anemia
    Marion, William
    Koppe, Tiago
    Chen, Chun-Chin
    Wang, Dahai
    Frenis, Katie
    Fierstein, Sara
    Sensharma, Prerana
    Aumais, Olivia
    Peters, Michael
    Ruiz-Torres, Sonya
    Chihanga, Tafadzwa
    Boettcher, Steffen
    Shimamura, Akiko
    Bauer, Daniel E.
    Schlaeger, Thorsten
    Wells, Susanne I. I.
    Ebert, Benjamin L. L.
    Starczynowski, Daniel
    da Rocha, Edroaldo Lummertz
    Rowe, R. Grant
    LEUKEMIA, 2023, 37 (08) : 1698 - 1708
  • [50] B-cell acute lymphoblastic leukemia in patients with germline RUNX1 mutations
    Six, Kathryn A.
    Gerdemann, Ulrike
    Brown, Anna L.
    Place, Andrew E.
    Cantor, Alan B.
    Kutny, Matthew A.
    Avagyan, Serine
    BLOOD ADVANCES, 2021, 5 (16) : 3199 - 3202