PUBLICATION
c-myb is involved in CML progression and is a therapeutic target in the zebrafish CML model
- Authors
- Ye, Y., Yang, X., Li, F., Liu, W., Zhang, W., Huang, Z.
- ID
- ZDB-PUB-221028-34
- Date
- 2022
- Source
- Animal models and experimental medicine 7(2): 136-144 (Journal)
- Registered Authors
- Zhang, Wenqing
- Keywords
- c-myb, chronic myeloid leukemia, flavopiridol, zebrafish model
- MeSH Terms
-
- Animals
- Animals, Genetically Modified*
- Antineoplastic Agents/pharmacology
- Antineoplastic Agents/therapeutic use
- Disease Models, Animal*
- Disease Progression*
- Flavonoids*/pharmacology
- Flavonoids*/therapeutic use
- Fusion Proteins, bcr-abl/genetics
- Fusion Proteins, bcr-abl/metabolism
- Imatinib Mesylate*/pharmacology
- Imatinib Mesylate*/therapeutic use
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive*/drug therapy
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive*/genetics
- Neutrophils/drug effects
- Neutrophils/metabolism
- Piperidines/pharmacology
- Piperidines/therapeutic use
- Protein Kinase Inhibitors/pharmacology
- Protein Kinase Inhibitors/therapeutic use
- Proto-Oncogene Proteins c-myb*/genetics
- Proto-Oncogene Proteins c-myb*/metabolism
- Zebrafish*
- PubMed
- 36300552 Full text @ Animal Model Exp Med
Citation
Ye, Y., Yang, X., Li, F., Liu, W., Zhang, W., Huang, Z. (2022) c-myb is involved in CML progression and is a therapeutic target in the zebrafish CML model. Animal models and experimental medicine. 7(2):136-144.
Abstract
Background Despite the success of tyrosine kinase inhibitors in chronic myeloid leukemia (CML) therapy, CML still faces the challenges of drug resistance and progression to blast crisis. Twenty-five percent of patients have imatinib resistance and treatment difficulties due to heterogeneity after progression, but little is known about the mechanism. A key transcription factor in hematopoiesis, MYB, has been reported to increase abnormally in several types of aggressive blood disorders including CML.
Methods This study used a zebrafish model to explore the relationship between BCR/ABL1 and c-myb in CML progression. A CML zebrafish model was crossed with a c-myb hyperactivity transgenic line.
Results It was found that both exogenous BCR/ABL1 and c-myb could up-regulate the expression of neutrophil-related genes. More seriously, neutrophil accumulation was observed when BCR/ABL1 was combined with c-myb overexpression. Further studies showed that c-myb may be one of the downstream targets of BCR/ABL1 and the effect of BCR/ABL1 on neutrophils was c-myb dependent. Taking advantage of this inheritable in vivo model, it was shown that a combination of imatinib and flavopiridol, a cyclin-dependent kinase inhibitor targeting MYB, could more effectively alleviate the aggressive phenotype of the double transgene line.
Conclusion In summary, this study suggests that c-myb acts downstream of BCR/ABL1 and is involved in CML progression and is therefore a risk factor and a valuable target for the treatment of CML progression. The model used in the study could be helpful in high-throughput drug screening in CML transformation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping