| Autor: |
Yaser Heshmati, Gözde Türköz, Marios Dimitriou, Aditya Harisankar, Johan Boström, Huan Cai, Nadir Kadri, Mikael Altun, Hong Qian, Julian Walfridsson |
| Rok vydání: |
2022 |
| Popis: |
Acute myeloid leukemia (AML) is an aggressive blood malignancy characterized by clonal accumulating of immature myeloid progenitors in the bone marrow and peripheral blood. Transcription factors are the most frequently mutated and dysregulated genes in AML and they have critical roles in AML pathogenesis and progression. In this study, we performed large-scale RNA interference screens in MLL-AF9 transformed AML cells and identified GTF2IRD1 as a novel transcription factor essential for the survival of various types of myeloid leukemic cells in vitro and in vivo, but not for primary normal hematopoietic cells. Inhibition of GTF2IRD1 reduced the frequency of primary childhood and adult AML cells, including cell populations enriched for leukemia-initiating cells. In animal models for AML, inhibition of GTF2IRD1 significantly delayed the disease progression. Inhibition of GTF2IRD1 caused an accumulation of quiescent AML cells in the G0 phase of the cell cycle but caused minor effects in apoptosis. In line with this, RNA sequencing analysis revealed a significant downregulation of E2F targets as a consequence of inhibition of GTF2IRD1. Taken together, we identified GTF2IRD1 as a transcription factor with a selective importance in AML and our findings may contribute to new therapeutic inventions for the disease. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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