دورية أكاديمية
New insights into the biology of acute myeloid leukemia with mutated NPM1.
العنوان: | New insights into the biology of acute myeloid leukemia with mutated NPM1. |
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المؤلفون: | Brunetti L; The Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, 77030, USA.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, 77030, USA.; Centro Ricerca Emato-Oncologica (CREO), Università degli Studi di Perugia, 06123, Perugia, Italy., Gundry MC; The Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, 77030, USA.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, 77030, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Goodell MA; The Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, 77030, USA. goodell@bcm.edu.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, 77030, USA. goodell@bcm.edu.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA. goodell@bcm.edu.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA. goodell@bcm.edu. |
المصدر: | International journal of hematology [Int J Hematol] 2019 Aug; Vol. 110 (2), pp. 150-160. Date of Electronic Publication: 2019 Jan 10. |
نوع المنشور: | Journal Article; Review |
اللغة: | English |
بيانات الدورية: | Publisher: Springer Japan Country of Publication: Japan NLM ID: 9111627 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1865-3774 (Electronic) Linking ISSN: 09255710 NLM ISO Abbreviation: Int J Hematol Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2008- : Tokyo : Springer Japan Original Publication: Amsterdam : Elsevier Science Publishers, c1991- |
مواضيع طبية MeSH: | Leukemia, Myeloid, Acute/*genetics , Neoplasm Proteins/*genetics , Nuclear Proteins/*genetics, Animals ; Cell Nucleolus/metabolism ; Cell Transformation, Neoplastic/genetics ; Cytoplasm/metabolism ; Frameshift Mutation ; Gene Expression Regulation, Leukemic ; Genes, Homeobox ; Genomic Instability ; Humans ; Leukemia, Experimental/genetics ; Leukemia, Myeloid, Acute/physiopathology ; Mice ; Mice, Transgenic ; Molecular Targeted Therapy ; Mutation, Missense ; Neoplasm Proteins/antagonists & inhibitors ; Neoplasm Proteins/chemistry ; Neoplasm Proteins/physiology ; Nuclear Proteins/antagonists & inhibitors ; Nuclear Proteins/chemistry ; Nuclear Proteins/physiology ; Nucleophosmin ; Protein Domains ; Protein Isoforms/chemistry ; Protein Isoforms/physiology ; Protein Transport ; Structure-Activity Relationship |
مستخلص: | Acute myeloid leukemia (AML), the most common acute leukemia in adults, increases exponentially with age. While a number of recent advances have improved treatment, high cure rates have not yet been achieved. Nucleophosmin (NPM1) is found mutated in nearly one-third of newly diagnosed cases and leads to NPM1 protein that is mislocalized to the cytoplasm instead of the nucleolus. If the mechanistic basis through which this mislocalization leads to malignancy could be revealed, this AML subtype may be targetable with new drugs. Here, we review the structure and functions of the normal and mutant forms of nucleophosmin. We discuss several recent studies that have shed light on the pathophysiology of NPM1 mutations. We discuss the importance of HOX gene misregulation in NPM1-mutated leukemias, as well as evidence for the reliance of mutated NPM1 on its continued nuclear export. Together, these aspects, as well as new tools to manipulate and study NPM1, open the door to new therapeutic strategies that may ultimately improve treatment of this common subtype of AML. |
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معلومات مُعتمدة: | R01 CA183252 United States CA NCI NIH HHS; R01 DK092883 United States DK NIDDK NIH HHS |
فهرسة مساهمة: | Keywords: AML; Acute myeloid leukemia; B23; HOX; NPM1; XPO1 |
المشرفين على المادة: | 0 (NPM1 protein, human) 0 (Neoplasm Proteins) 0 (Npm1 protein, mouse) 0 (Nuclear Proteins) 0 (Protein Isoforms) 117896-08-9 (Nucleophosmin) |
تواريخ الأحداث: | Date Created: 20190112 Date Completed: 20200109 Latest Revision: 20211204 |
رمز التحديث: | 20240628 |
DOI: | 10.1007/s12185-018-02578-7 |
PMID: | 30632059 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1865-3774 |
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DOI: | 10.1007/s12185-018-02578-7 |