骨髓增生性肿瘤动物模型。
Myeloproliferative neoplasm animal models.
机构信息
Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
出版信息
Hematol Oncol Clin North Am. 2012 Oct;26(5):1065-81. doi: 10.1016/j.hoc.2012.07.007. Epub 2012 Aug 21.
Abstract
Myeloproliferative neoplasm (MPN) animal models accurately re-capitulate human disease in mice and have been an important tool for the study of MPN biology and therapy. Transplantation of BCR-ABL transduced bone marrow into irradiated syngeneic mice established the field of MPN animal modeling. Genetically engineered MPN animal models have enabled detailed characterization of the effects of specific MPN-associated genetic abnormalities on hematopoietic stem and progenitor cells (HSPCs). Xenograft models have allowed the study of primary human MPN-propagating cells in vivo. JAK2V617F, the most common molecular abnormality in BCR-ABL negative MPN, has been extensively studied using retroviral, transgenic, knock-in and xenograft models.
摘要
骨髓增殖性肿瘤（MPN）动物模型在小鼠中准确地再现了人类疾病，是研究 MPN 生物学和治疗的重要工具。BCR-ABL 转导的骨髓移植到辐照同基因小鼠中，建立了 MPN 动物模型领域。基因工程 MPN 动物模型使我们能够详细描述特定的 MPN 相关遗传异常对造血干细胞和祖细胞（HSPCs）的影响。异种移植模型允许在体内研究原发性人类 MPN 传播细胞。JAK2V617F 是 BCR-ABL 阴性 MPN 中最常见的分子异常，已广泛使用逆转录病毒、转基因、基因敲入和异种移植模型进行研究。
相似文献
1
Myeloproliferative neoplasm animal models.
Hematol Oncol Clin North Am. 2012 Oct;26(5):1065-81. doi: 10.1016/j.hoc.2012.07.007. Epub 2012 Aug 21.
2
3
4
Overview of Transgenic Mouse Models of Myeloproliferative Neoplasms (MPNs).
Curr Protoc Pharmacol. 2017 Jun 22;77:14.40.1-14.40.19. doi: 10.1002/cpph.23.
5
The Tel-Abl (ETV6-Abl) tyrosine kinase, product of complex (9;12) translocations in human leukemia, induces distinct myeloproliferative disease in mice.
Blood. 2002 Jun 15;99(12):4568-77. doi: 10.1182/blood-2001-12-0244.
6
Description of a knock-in mouse model of JAK2V617F MPN emerging from a minority of mutated hematopoietic stem cells.
Blood. 2019 Dec 26;134(26):2383-2387. doi: 10.1182/blood.2019001163.
7
Myeloproliferative neoplasm induced by constitutive expression of JAK2V617F in knock-in mice.
Blood. 2010 Aug 5;116(5):783-7. doi: 10.1182/blood-2009-12-257063. Epub 2010 May 14.
8
Inducible expression of BCR/ABL using human CD34 regulatory elements results in a megakaryocytic myeloproliferative syndrome.
Blood. 2003 Nov 1;102(9):3363-70. doi: 10.1182/blood-2003-03-0768. Epub 2003 Jul 10.
9
Deletion of Stat3 enhances myeloid cell expansion and increases the severity of myeloproliferative neoplasms in Jak2V617F knock-in mice.
Leukemia. 2015 Oct;29(10):2050-61. doi: 10.1038/leu.2015.116. Epub 2015 May 18.
10
[Progress of study on JAK2V617F mutation in myeloproliferative neoplasm].
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2011 Oct;19(5):1329-33.
引用本文的文献
1
Mesenchymal stromal cells from myeloproliferative neoplasms support healthy and malignant hematopoiesis in a humanized scaffold model in vivo.
Hemasphere. 2025 Aug 22;9(8):e70185. doi: 10.1002/hem3.70185. eCollection 2025 Aug.
2
Complementary and countervailing actions of Jak2 and Ikk2 in hematopoiesis in mice.
Exp Hematol. 2023 Dec;128:48-66. doi: 10.1016/j.exphem.2023.08.005. Epub 2023 Aug 21.
3
Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer.
Signal Transduct Target Ther. 2023 May 19;8(1):204. doi: 10.1038/s41392-023-01468-7.
4
Biology and therapeutic targeting of molecular mechanisms in MPNs.
Blood. 2023 Apr 20;141(16):1922-1933. doi: 10.1182/blood.2022017416.
5
Molecular pathogenesis of the myeloproliferative neoplasms.
J Hematol Oncol. 2021 Jun 30;14(1):103. doi: 10.1186/s13045-021-01116-z.
6
Inflammatory Pathophysiology as a Contributor to Myeloproliferative Neoplasms.
Front Immunol. 2021 Jun 1;12:683401. doi: 10.3389/fimmu.2021.683401. eCollection 2021.
7
Induced pluripotent stem cell models of myeloid malignancies and clonal evolution.
Stem Cell Res. 2021 Apr;52:102195. doi: 10.1016/j.scr.2021.102195. Epub 2021 Jan 26.
8
Metabolic Vulnerabilities and Epigenetic Dysregulation in Myeloproliferative Neoplasms.
Front Immunol. 2020 Nov 30;11:604142. doi: 10.3389/fimmu.2020.604142. eCollection 2020.
9
Heterogeneous bone-marrow stromal progenitors drive myelofibrosis via a druggable alarmin axis.
Cell Stem Cell. 2021 Apr 1;28(4):637-652.e8. doi: 10.1016/j.stem.2020.11.004. Epub 2020 Dec 9.
10
Murine Models of Myelofibrosis.
Cancers (Basel). 2020 Aug 23;12(9):2381. doi: 10.3390/cancers12092381.
本文引用的文献
1
Distinct roles for long-term hematopoietic stem cells and erythroid precursor cells in a murine model of Jak2V617F-mediated polycythemia vera.
Blood. 2012 Jul 5;120(1):166-72. doi: 10.1182/blood-2012-01-402396. Epub 2012 May 24.
2
Altered microenvironmental regulation of leukemic and normal stem cells in chronic myelogenous leukemia.
Cancer Cell. 2012 Apr 17;21(4):577-92. doi: 10.1016/j.ccr.2012.02.018.
3
Genetic and pharmacologic inhibition of β-catenin targets imatinib-resistant leukemia stem cells in CML.
Cell Stem Cell. 2012 Apr 6;10(4):412-24. doi: 10.1016/j.stem.2012.02.017.
4
Efficacy of vorinostat in a murine model of polycythemia vera.
Blood. 2012 Apr 19;119(16):3779-89. doi: 10.1182/blood-2011-02-336743. Epub 2012 Mar 9.
5
Polycomb repressive complex 2 is required for MLL-AF9 leukemia.
Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):5028-33. doi: 10.1073/pnas.1202258109. Epub 2012 Mar 6.
6
Genetic resistance to JAK2 enzymatic inhibitors is overcome by HSP90 inhibition.
J Exp Med. 2012 Feb 13;209(2):259-73. doi: 10.1084/jem.20111694. Epub 2012 Jan 23.
7
Critical requirement for Stat5 in a mouse model of polycythemia vera.
Blood. 2012 Apr 12;119(15):3539-49. doi: 10.1182/blood-2011-03-345215. Epub 2011 Dec 5.
8
Dnmt3a is essential for hematopoietic stem cell differentiation.
Nat Genet. 2011 Dec 4;44(1):23-31. doi: 10.1038/ng.1009.
9
IL-6 controls leukemic multipotent progenitor cell fate and contributes to chronic myelogenous leukemia development.
Cancer Cell. 2011 Nov 15;20(5):661-73. doi: 10.1016/j.ccr.2011.10.012.
10
EXEL-8232, a small-molecule JAK2 inhibitor, effectively treats thrombocytosis and extramedullary hematopoiesis in a murine model of myeloproliferative neoplasm induced by MPLW515L.
Leukemia. 2012 Apr;26(4):720-7. doi: 10.1038/leu.2011.261. Epub 2011 Oct 18.
Zotero 插件