AML1/RUNX1 point mutation possibly promotes leukemic transformation in myeloproliferative neoplasms
| Autor: | Hironori Harada, Akiro Kimura, Jun Imagawa, Yuka Harada, Ye Ding |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Myeloid Green Fluorescent Proteins Immunoblotting Immunology CD34 Antigens CD34 Biology Transfection Biochemistry Leukemogenic chemistry.chemical_compound hemic and lymphatic diseases medicine Humans Point Mutation Progenitor cell Cells Cultured Aged Cell Proliferation Aged 80 and over Leukemia Myeloproliferative Disorders Cell Biology Hematology Middle Aged medicine.disease Cell Transformation Neoplastic Retroviridae medicine.anatomical_structure RUNX1 chemistry Core Binding Factor Alpha 2 Subunit Cancer research Female Stem cell |
| Zdroj: | Blood. 114:5201-5205 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2009-06-223982 |
| Popis: | Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by proliferation of one or more myeloid cell lineages. Some patients exhibit leukemic transformation (LT) by unknown mechanisms, and chemotherapy may increase the risk of LT. To clarify the molecular mechanisms of LT, gene alterations involved in LT from patients in the chronic phase (CP) of MPNs were identified. Among 18 patients who progressed to leukemia, AML1/RUNX1 mutations were detected in 5 patients at the LT but in none at the CP. To investigate the leukemogenic effect of AML1/RUNX1 mutants, the AML1D171N mutant was transduced into CD34+ cells from patients in the CP of MPNs. The D171N transduction resulted in proliferation of immature myeloid cells, enhanced self-renewal capacity, and proliferation of primitive progenitors. Taken together, these results indicate that AML1/RUNX1 point mutations may have a leukemogenic potential in MPN stem cells, and they may promote leukemic transformation in MPN. |
| Databáze: | OpenAIRE |
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