急性髓系白血病发病机制中的肾母细胞瘤1基因突变
Wilms tumor 1 mutations in the pathogenesis of acute myeloid leukemia.
作者信息
Rampal Raajit, Figueroa Maria E
机构信息
Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA
出版信息
Haematologica. 2016 Jun;101(6):672-9. doi: 10.3324/haematol.2015.141796.
Abstract
Wilms tumor 1 (WT1) has long been implicated in acute myeloid leukemia. It has been described to be both overexpressed and mutated in different forms of acute myeloid leukemia, and overexpression has been reported to play a prognostic role in this disease. However, the precise mechanism through which WT1 may play a role in leukemogenesis has remained elusive. In recent years, new evidence has emerged that points towards a novel role of WT1 mutations in the deregulation of epigenetic programs in leukemic cells through its interaction with TET proteins. Herein we review the current status of the field and its therapeutic and prognostic implications in acute myeloid leukemia.
摘要
肾母细胞瘤1（WT1）长期以来一直被认为与急性髓系白血病有关。在不同类型的急性髓系白血病中，WT1被描述为既过度表达又发生突变，并且据报道其过度表达在这种疾病中具有预后作用。然而，WT1在白血病发生过程中发挥作用的确切机制仍不清楚。近年来，新的证据表明，WT1突变通过与TET蛋白相互作用，在白血病细胞表观遗传程序失调中发挥新的作用。在此，我们综述了该领域的现状及其在急性髓系白血病中的治疗和预后意义。
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本文引用的文献
1
WT1 vaccination in AML and MDS: A pilot trial with synthetic analog peptides.
Am J Hematol. 2015 Jul;90(7):602-7. doi: 10.1002/ajh.24014. Epub 2015 May 3.
2
Review of the Results of WT1 Peptide Vaccination Strategies for Myelodysplastic Syndromes and Acute Myeloid Leukemia from Nine Different Studies.
Front Immunol. 2015 Feb 4;6:36. doi: 10.3389/fimmu.2015.00036. eCollection 2015.
3
Presence of isocitrate dehydrogenase mutations may predict clinical response to hypomethylating agents in patients with acute myeloid leukemia.
Am J Hematol. 2015 May;90(5):E77-9. doi: 10.1002/ajh.23965. Epub 2015 Feb 27.
4
WT1 recruits TET2 to regulate its target gene expression and suppress leukemia cell proliferation.
Mol Cell. 2015 Feb 19;57(4):662-673. doi: 10.1016/j.molcel.2014.12.023. Epub 2015 Jan 15.
5
DNA hydroxymethylation profiling reveals that WT1 mutations result in loss of TET2 function in acute myeloid leukemia.
Cell Rep. 2014 Dec 11;9(5):1841-1855. doi: 10.1016/j.celrep.2014.11.004. Epub 2014 Dec 4.
6
Mutant WT1 is associated with DNA hypermethylation of PRC2 targets in AML and responds to EZH2 inhibition.
Blood. 2015 Jan 8;125(2):316-26. doi: 10.1182/blood-2014-03-566018. Epub 2014 Nov 14.
7
TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients.
Blood. 2014 Oct 23;124(17):2705-12. doi: 10.1182/blood-2014-06-582809. Epub 2014 Sep 15.
8
Targeting the intracellular WT1 oncogene product with a therapeutic human antibody.
Sci Transl Med. 2013 Mar 13;5(176):176ra33. doi: 10.1126/scitranslmed.3005661.
9
Prognostic relevance of integrated genetic profiling in acute myeloid leukemia.
N Engl J Med. 2012 Mar 22;366(12):1079-89. doi: 10.1056/NEJMoa1112304. Epub 2012 Mar 14.
10
Active specific immunotherapy targeting the Wilms' tumor protein 1 (WT1) for patients with hematological malignancies and solid tumors: lessons from early clinical trials.
Oncologist. 2012;17(2):250-9. doi: 10.1634/theoncologist.2011-0240. Epub 2012 Jan 30.
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