MLLT6在白血病中的研究进展

doi:10.11904/j.issn.1002-3070.2018.02.009

摘要/Abstract

摘要： MLLT6又称为AF17(ALL1 fused gene from chromosome 17 protein),位于人类17号染色体长臂2区1带(17q21),最初在白血病中作为MLL的伙伴基因被分离出来。有文献报道MLLT6在人体内具有维持血压稳定的功能。同时MLLT6作为癌基因或和混合谱系白血病(Mixed lineage leukemia,MLL)的基因融合(t(11;17)(q23;q21)等)协同促进急性骨髓性白血病(AML)的发生发展。本文就MLLT6及MLL-MLLT6融合蛋白在白血病中的研究进展进行全面概述。

关键词: MLLT6, MLL-MLLT6融合蛋白, 白血病, 血压稳定

Abstract: MLLT6(Myeloid/Lymphoid or mixed-lineage leukemia(Trithorax homolog,Drosophila);Translocated to,6),also known as AF17(ALL1 fused gene from chromosome 17 protein)and located in chromosome 17 long arm 2 zone 1 band(17q21),was originally isolated as a MLL partner gene in leukemia.It has been reported that MLLT6 has the function of maintaining blood pressure stability.MLLT6 synergistically promotes the development of acute myeloid leukemia(AML)as an oncogene or a gene fusion with mixed lineage leukemia(t(11;17)(q23;q21)).This article provides a comprehensive overview of the research progress of MLLT6 and MLL-MLLT6 fusion protein in leukemia.

Key words: MLLT6, MLL-MLLT6 fusion protein, Leukemia, Blood pressure homeostasis

中图分类号:

R733.7

李毅鹏, 张鑫宇, 吕涵柠, 孙立春. MLLT6在白血病中的研究进展[J]. 实用肿瘤学杂志, 2018, 32(2): 135-139.

LI Yipeng, ZHANG Xinyu, LV Hanning, SUN Lichun. Research progression of MLLT6 in leukemia[J]. PRACTICAL ONCOLOGY JOURNAL, 2018, 32(2): 135-139.

参考文献

1 Prasad R,Leshkowitz D,Gu Y,et al.Leucine-zipper dimerization motif encoded by the AF17 gene fused to ALL-1(MLL)in acute leukemia[J].Proc Natl Acad Sci U S A,1994,91(17):8107-8111.
2 Zhang Z,Huang L,Reisenauer MR,et al.Widely expressed Af17 is likely not required for embryogenesis,hematopoiesis,and animal survival[J].Genesis,2010,48(12):693-706.
3 Beronja S,Janki P,Heller E,et al.RNAi screens in mice identify physiological regulators of oncogenic growth[J].Nature,2013,501(7466):185-190.
4 Strehl S,Konig M,Meyer C,et al.Molecular dissection of t(11;17)in acute myeloid leukemia reveals a variety of gene fusions with heterogeneous fusion transcripts and multiple splice variants[J].Genes Chromosomes Cancer,2006,45(11):1041-1049.
5 Chen L,Wu H,Pochynyuk OM,et al.Af17 deficiency increases sodium excretion and decreases blood pressure[J].J Am Soc Nephrol,2011,22(6):1076-1086.
6 Chen L,Zhang X,Zhang W.Regulation of αENaC transcription[J].Vitam Horm,2015,98:101-135.
7 Kone BC.Epigenetics and the control of the collecting duct epithelial sodium channel[J].Semin Nephrol,2013,33(4):383-391.
8 Reisenauer MR,Anderson M,Huang L,et al.AF17 competes with AF9 for binding to Dot1a to up-regulate transcription of epithelial Na⁺ channel alpha[J].J Biol Chem,2009,284(51):35659-35669.
9 Stulemeijer IJ,De Vos D,van Harten K,et al.Dot1 histone methyltransferases share a distributive mechanism but have highly diverged catalytic properties[J].Sci Rep,2015,5:9824.
10 Vlaming H,Molenaar TM,van Welsem T,et al.Direct screening for chromatin status on DNA barcodes in yeast delineates the regulome of H3K79 methylation by Dot1[J].Elife,2016,5:e18919.
11 Zhang W.Epigenetics of epithelial Na⁺channel-dependent sodium uptake and blood pressure regulation[J].World J Nephrol,2015,4(3):363-366.
12 Lou Y,Zhang F,Luo Y,et al.Serum and glucocorticoid regulated kinase 1 in sodium homeostasis[J].Int J Mol Sci,2016,17(8):1307.
13 高文龙.DOT1和组蛋白H3Lysine79甲基化在小鼠卵母细胞减数分裂中的作用[D].南京:南京农业大学,2007.
14 高文龙,刘红林.DOT1一类新的组蛋白赖氨酸甲基转移酶[J].遗传,2007,29(12):1449-1454.
15 Sabatino M,Rotili D,Patsilinakos A,et al.Disruptor of telomeric silencing 1-like(DOT1L):disclosing a new class of non-nucleoside inhibitors by means of ligand-based and structure-based approaches[J].J Comput Aided Mol Des,2018[Epub ahead of print].
16 Deshpande AJ,Deshpande A,Sinha AU,et al.AF10 regulates progressive H3K79 methylation and HOX gene expression in diverse AML subtypes[J].Cancer Cell,2014,26(6):896-908.
17 Chen S,Yang Z,Wilkinson AW,et al.The PZP domain of AF10 senses unmodified H3K27 to regulate DOT1L-mediated methylation of H3K79[J].Mol Cell,2015,60(2):319-327.
18 Nichol JN,Dupere-Richer D,Ezponda T,et al.H3K27 methylation:A focal point of epigenetic deregulation in cancer[J].Adv Cancer Res,2016,131:59-95.
19 Basavapathruni A,Olhava EJ,Daigle SR,et al.Nonclinical pharmacokinetics and metabolism of EPZ-5676,a novel DOT1L histone methyltransferase inhibitor[J].Biopharm Drug Dispos,2014,35(4):237-252.
20 Marschalek R.Systematic classification of mixed-lineage leukemia fusion partners predicts additional cancer pathways[J].Ann Lab Med,2016,36(2):85-100.
21 Okuda H,Stanojevic B,Kanai A,et al.Cooperative gene activation by AF4 and DOT1L drives MLL-rearranged leukemia[J].J Clin Invest,2017,127(5):1918-1931.
22 Chen CW,Armstrong SA.Targeting DOT1L and HOX gene expression in MLL-rearranged leukemia and beyond[J].Exp Hematol,2015,43(8):673-684.
23 Smith E,Lin C,Shilatifard A.The super elongation complex(SEC)and MLL in development and disease[J].Genes Dev,2011,25(7):661-672.
24 张祝,黄涵柽,高开波.DOT1L对急性白血病靶位研究与靶向治疗的意义与前景[J].湖北民族学院学报(医学版),2017(3):53-57.
25 Mohan M,Herz HM,Takahashi YH,et al.Linking H3K79 trimethylation to Wnt signaling through a novel Dot1-containing complex(DotCom)[J].Genes Dev,2010,24(6):574-589.
26 Undi RB,Gutti U,Sahu I,et al.Wnt signaling:Role in regulation of haematopoiesis[J].Indian J Hematol Blood Transfus,2016,32(2):123-134.
27 Yu S,Li F,Xing S,et al.Hematopoietic and leukemic stem cells have distinct dependence on Tcf1 and Lef1 transcription factors[J].J Biol Chem,2016,291(21):11148-11160.
28 Monga SP.beta-Catenin signaling and roles in liver homeostasis,injury,and tumorigenesis[J].Gastroenterology,2015,148(7):1294-1310.
29 Voronkov A,Krauss S.Wnt/beta-catenin signaling and small molecule inhibitors[J].Curr Pharm Des,2013,19(4):634-664.
30 Lin YM,Ono K,Satoh S,et al.Identification of AF17 as a downstream gene of the beta-catenin/T-cell factor pathway and its involvement in colorectal carcinogenesis[J].Cancer Res,2001,61(17):6345-6349.
31 Winters AC,Bernt KM.MLL-rearranged leukemias-an update on science and clinical approaches[J].Front Pediatr,2017,5:4.
32 Yang H,Huang S,Zhu CY,et al.The superiority of allogeneic hematopoietic stem cell transplantation over chemotherapy alone in the treatment of acute myeloid leukemia patients with mixed lineage leukemia(MLL)rearrangements[J].Med Sci Monit,2016,22:2315-2323.
33 陈成坚,汪明春,李明,等.急性白血病11q23/MLL基因易位重排及其临床意义[J].临床血液学杂志,2005,18(6):30-33.
34 Meyer C,Kowarz E,Hofmann J,et al.New insights to the MLL recombinome of acute leukemias[J].Leukemia,2009,23(8):1490-1499.
35 Yang H,Cao T,Gao L,et al.The incidence and distribution characteristics of MLL rearrangements in Chinese acute myeloid leukemia patients by multiplex nested RT-PCR[J].Technol Health Care,2017,25(S1):259-265.
36 Suzukawa K,Shimizu S,Nemoto N,et al.Identification of a chromosomal breakpoint and detection of a novel form of an MLL-AF17 fusion transcript in acute monocytic leukemia with t(11;17)(q23;q21)[J].Int J Hematol,2005,82(1):38-41.
37 Martin ME,Milne TA,Bloyer S,et al.Dimerization of MLL fusion proteins immortalizes hematopoietic cells[J].Cancer Cell,2003,4(3):197-207.
38 Daigle SR,Olhava EJ,Therkelsen CA,et al.Potent inhibition of DOT1L as treatment of MLL-fusion leukemia[J].Blood,2013,122(6):1017-1025.
39 Borkin D,He S,Miao H,et al.Pharmacologic inhibition of the Menin-MLL interaction blocks progression of MLL leukemia in vivo[J].Cancer Cell,2015,27(4):589-602.
40 Kerry J,Godfrey L,Repapi E,et al.MLL-AF4 spreading identifies binding sites that are distinct from super-enhancers and that govern sensitivity to DOT1L inhibition in leukemia[J].Cell Rep,2017,18(2):482-495.

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