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| Format: | Artículo científico |
| Language: | en |
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Proceedings of the National Academy of Sciences of the United States of America
2025
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| Online Access: | https://pubmed.ncbi.nlm.nih.gov/40020188/ |
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| _version_ | 1868266237316825088 |
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| author | Xu, Song'en Hong, Jiaxin Dongye, Meimei Lin, Jiehao Xue, Rongtao Huang, Zhibin Xu, Jin Zhang, Yiyue Leung, Anskar Yu-Hung Shen, Juan Zhang, Wenqing Liu, Wei |
| author_facet | Xu, Song'en Hong, Jiaxin Dongye, Meimei Lin, Jiehao Xue, Rongtao Huang, Zhibin Xu, Jin Zhang, Yiyue Leung, Anskar Yu-Hung Shen, Juan Zhang, Wenqing Liu, Wei Xu, Song'en Hong, Jiaxin Dongye, Meimei Lin, Jiehao Xue, Rongtao Huang, Zhibin Xu, Jin Zhang, Yiyue Leung, Anskar Yu-Hung Shen, Juan Zhang, Wenqing Liu, Wei |
| collection | PubMed - marine biology |
| contents | The synergistic effect of c-Myb hyperactivation and Pu.1 deficiency induces Pelger-Huët anomaly and promotes sAML. Xu, Song'en Hong, Jiaxin Dongye, Meimei Lin, Jiehao Xue, Rongtao Huang, Zhibin Xu, Jin Zhang, Yiyue Leung, Anskar Yu-Hung Shen, Juan Zhang, Wenqing Liu, Wei Animals Zebrafish Trans-Activators Proto-Oncogene Proteins c-myb Proto-Oncogene Proteins Leukemia, Myeloid, Acute Humans Myelodysplastic Syndromes Mutation Male Proto-Oncogene Protein Spi-1 Approximately 30% of patients with myelodysplastic syndrome (MDS) progress to secondary acute myeloid leukemia (sAML) via accumulating gene mutations. Genomic analyses reveal a complex interplay among mutant genes, with co-occurring and mutually exclusive patterns. Hyperactivation of c-MYB and deficiency of PU.1 have been linked to myeloid disorders. We report a case of AML with concurrent and mutations, exhibiting early onset, high blast count, chemo-resistance, indicating high-risk features, along with elevated Pelger-Huët anomaly (PHA). However, the synergistic mechanism of and in sAML remains unclear. Using c-Myb-hyperactivation and Pu.1-deficient double-strain () zebrafish, we investigated MDS/sAML progression. Surprisingly, the double mutant exhibited a distinct type of neutrophil resembling clinical PHA cells and demonstrated a higher rate of MDS/sAML transformation. Further expression analysis revealed reduced expression in double-mutant zebrafish. Knockdown of resulted in PHA and increased blast cells, while overexpression of in reduced PHA cell level. This suggests that c-Myb hyperactivation and Pu.1 deficiency synergistically reduce expression, inducing the development of PHA-like neutrophils and promoting MDS/sAML progression in zebrafish. Moreover, coadministration of cell cycle inhibitor cytarabine (Ara-C) and the differential inducer all-trans retinoic acid (ATRA) could effectively relieve the neutrophil expansion and PHA symptoms in zebrafish. Our findings revealed that c-Myb hyperactivation and Pu.1 deficiency played a synergistic role in sAML development and suggests a phenotypic association between the emergence of PH-like cells and the transformation to sAML. Furthermore, zebrafish might serve as a suitable sAML model for drug screening. |
| format | Artículo científico |
| id | pubmed_40020188 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Proceedings of the National Academy of Sciences of the United States of America |
| record_format | pubmed |
| spellingShingle | The synergistic effect of c-Myb hyperactivation and Pu.1 deficiency induces Pelger-Huët anomaly and promotes sAML. Xu, Song'en Hong, Jiaxin Dongye, Meimei Lin, Jiehao Xue, Rongtao Huang, Zhibin Xu, Jin Zhang, Yiyue Leung, Anskar Yu-Hung Shen, Juan Zhang, Wenqing Liu, Wei Animals Zebrafish Trans-Activators Proto-Oncogene Proteins c-myb Proto-Oncogene Proteins Leukemia, Myeloid, Acute Humans Myelodysplastic Syndromes Mutation Male Proto-Oncogene Protein Spi-1 The synergistic effect of c-Myb hyperactivation and Pu.1 deficiency induces Pelger-Huët anomaly and promotes sAML. Xu, Song'en Hong, Jiaxin Dongye, Meimei Lin, Jiehao Xue, Rongtao Huang, Zhibin Xu, Jin Zhang, Yiyue Leung, Anskar Yu-Hung Shen, Juan Zhang, Wenqing Liu, Wei Animals Zebrafish Trans-Activators Proto-Oncogene Proteins c-myb Proto-Oncogene Proteins Leukemia, Myeloid, Acute Humans Myelodysplastic Syndromes Mutation Male Proto-Oncogene Protein Spi-1 Approximately 30% of patients with myelodysplastic syndrome (MDS) progress to secondary acute myeloid leukemia (sAML) via accumulating gene mutations. Genomic analyses reveal a complex interplay among mutant genes, with co-occurring and mutually exclusive patterns. Hyperactivation of c-MYB and deficiency of PU.1 have been linked to myeloid disorders. We report a case of AML with concurrent and mutations, exhibiting early onset, high blast count, chemo-resistance, indicating high-risk features, along with elevated Pelger-Huët anomaly (PHA). However, the synergistic mechanism of and in sAML remains unclear. Using c-Myb-hyperactivation and Pu.1-deficient double-strain () zebrafish, we investigated MDS/sAML progression. Surprisingly, the double mutant exhibited a distinct type of neutrophil resembling clinical PHA cells and demonstrated a higher rate of MDS/sAML transformation. Further expression analysis revealed reduced expression in double-mutant zebrafish. Knockdown of resulted in PHA and increased blast cells, while overexpression of in reduced PHA cell level. This suggests that c-Myb hyperactivation and Pu.1 deficiency synergistically reduce expression, inducing the development of PHA-like neutrophils and promoting MDS/sAML progression in zebrafish. Moreover, coadministration of cell cycle inhibitor cytarabine (Ara-C) and the differential inducer all-trans retinoic acid (ATRA) could effectively relieve the neutrophil expansion and PHA symptoms in zebrafish. Our findings revealed that c-Myb hyperactivation and Pu.1 deficiency played a synergistic role in sAML development and suggests a phenotypic association between the emergence of PH-like cells and the transformation to sAML. Furthermore, zebrafish might serve as a suitable sAML model for drug screening. |
| title | The synergistic effect of c-Myb hyperactivation and Pu.1 deficiency induces Pelger-Huët anomaly and promotes sAML. |
| topic | Animals Zebrafish Trans-Activators Proto-Oncogene Proteins c-myb Proto-Oncogene Proteins Leukemia, Myeloid, Acute Humans Myelodysplastic Syndromes Mutation Male Proto-Oncogene Protein Spi-1 |
| url | https://pubmed.ncbi.nlm.nih.gov/40020188/ |