The molecular basis of myeloid malignancies
| Autor: | Jiro Kitaura, Katsuhiro Togami, Reina Nagase, Daichi Inoue, Naoko Okochi-Watanabe, Makoto Saika, Tomofusa Fukuyama, Yutaka Enomoto, Noriko Doki, Toshio Kitamura, Kimihito Cojin Kawabata, Tomoyuki Uchida, Fumio Nakahara, Yang Lu, Toshihiko Oki, Naoko Kato, Kumi Izawa, Yuki Kagiyama, Yukiko Komeno, Y Hayashi, Sayuri Horikawa |
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| Rok vydání: | 2014 |
| Předmět: |
Myeloid
Cohesin complex myeloproliferative neoplasm Fusion Proteins bcr-abl General Physics and Astronomy epigenetic factors Review acute myeloid leukemia Biology medicine.disease_cause Epigenesis Genetic splicing Mice chemistry.chemical_compound hemic and lymphatic diseases medicine Animals Humans Myeloproliferative neoplasm Cell Proliferation Genetics Mutation Myelodysplastic syndromes Myeloid leukemia General Medicine mutations medicine.disease myelodysplastic syndromes Leukemia Myeloid Acute Leukemia Cell Transformation Neoplastic medicine.anatomical_structure RUNX1 chemistry Hematologic Neoplasms General Agricultural and Biological Sciences |
| Zdroj: | Proceedings of the Japan Academy. Series B, Physical and Biological Sciences |
| ISSN: | 1349-2896 0386-2208 |
| DOI: | 10.2183/pjab.90.389 |
| Popis: | Myeloid malignancies consist of acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and myeloproliferative neoplasm (MPN). The latter two diseases have preleukemic features and frequently evolve to AML. As with solid tumors, multiple mutations are required for leukemogenesis. A decade ago, these gene alterations were subdivided into two categories: class I mutations stimulating cell growth or inhibiting apoptosis; and class II mutations that hamper differentiation of hematopoietic cells. In mouse models, class I mutations such as the Bcr-Abl fusion kinase induce MPN by themselves and some class II mutations such as Runx1 mutations induce MDS. Combinations of class I and class II mutations induce AML in a variety of mouse models. Thus, it was postulated that hematopoietic cells whose differentiation is blocked by class II mutations would autonomously proliferate with class I mutations leading to the development of leukemia. Recent progress in high-speed sequencing has enabled efficient identification of novel mutations in a variety of molecules including epigenetic factors, splicing factors, signaling molecules and proteins in the cohesin complex; most of these are not categorized as either class I or class II mutations. The functional consequences of these mutations are now being extensively investigated. In this article, we will review the molecular basis of hematological malignancies, focusing on mouse models and the interfaces between these models and clinical findings, and revisit the classical class I/II hypothesis. |
| Databáze: | OpenAIRE |
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