Npm1-KO Mouse

Npm1, also known as nucleophosmin 1, encodes a multifunctional protein with prominent nucleolar localization that shuttles between the nucleus and cytoplasm [1,2,3,4,5,6,7]. It acts as a histone chaperone and is involved in multiple cellular functions such as ribosome biogenesis, chromatin remodeling, genomic stability, cell cycle progression, and apoptosis [6,7]. Npm1-mutated acute myeloid leukemia (AML) is a distinct entity in the hematopoietic neoplasms classification, as Npm1 mutations are the most common genetic lesion in adult AML, occurring in about one-third of cases [1,3,4,5].

Mouse models of Npm1 mutations have been studied to understand the biological functions of the mutant protein. The Npm1 mutant undergoes C-terminus changes leading to its cytoplasmic delocalization in leukemic cells [6]. Studies have shown that Npm1-mutated cells rely on overexpression of HOX/MEIS1, which is related to the aberrant cytoplasmic localization of mutant Npm1 protein (Npm1c) [3]. This finding may explain the promising response of Npm1-mutated AML to novel agents like menin inhibitors and second-generation XPO1 inhibitors [3].

In conclusion, Npm1 is crucial for normal cellular functions, and its mutation is highly significant in AML. Mouse models of Npm1 mutations have been instrumental in revealing the biological mechanisms underlying Npm1-mutated AML, such as the role of HOX/MEIS1 overexpression, which may guide the development of new therapeutic strategies for this disease [3,6].

References:

1. Falini, Brunangelo, Brunetti, Lorenzo, Sportoletti, Paolo, Martelli, Maria Paola. . NPM1-mutated acute myeloid leukemia: from bench to bedside. In Blood, 136, 1707-1721. doi:10.1182/blood.2019004226. https://pubmed.ncbi.nlm.nih.gov/32609823/

2. Hindley, Andrew, Catherwood, Mark Alexander, McMullin, Mary Frances, Mills, Ken I. 2021. Significance of NPM1 Gene Mutations in AML. In International journal of molecular sciences, 22, . doi:10.3390/ijms221810040. https://pubmed.ncbi.nlm.nih.gov/34576201/

3. Patel, Sanjay S. 2023. NPM1-Mutated Acute Myeloid Leukemia: Recent Developments and Open Questions. In Pathobiology : journal of immunopathology, molecular and cellular biology, 91, 18-29. doi:10.1159/000530253. https://pubmed.ncbi.nlm.nih.gov/36944324/

4. Patel, Sanjay S, Kluk, Michael J, Weinberg, Olga K. . NPM1 Biology in Myeloid Neoplasia. In Current hematologic malignancy reports, 15, 350-359. doi:10.1007/s11899-020-00592-3. https://pubmed.ncbi.nlm.nih.gov/32494951/

5. Ishikawa, Yuichi, Ushijima, Yoko, Kiyoi, Hitoshi. 2024. Recent advances in AML with mutated NPM1. In International journal of hematology, 120, 556-565. doi:10.1007/s12185-024-03835-8. https://pubmed.ncbi.nlm.nih.gov/39174699/

6. Falini, Brunangelo, Sorcini, Daniele, Perriello, Vincenzo Maria, Sportoletti, Paolo. 2024. Functions of the native NPM1 protein and its leukemic mutant. In Leukemia, 39, 276-290. doi:10.1038/s41375-024-02476-4. https://pubmed.ncbi.nlm.nih.gov/39690184/

7. Karimi Dermani, Fateme, Gholamzadeh Khoei, Saeideh, Afshar, Saeid, Amini, Razieh. 2021. The potential role of nucleophosmin (NPM1) in the development of cancer. In Journal of cellular physiology, 236, 7832-7852. doi:10.1002/jcp.30406. https://pubmed.ncbi.nlm.nih.gov/33959979/