An aging mouse model of human chronic myeloid leukemia
| Autor: | Richard Ermel, WenYong Chen, Alison Buck, Young L. Kim, Taisen Hao, Zhiqiang Wang, Steven Vonderfecht, Chunxiao Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Anemia Fusion Proteins bcr-abl Bone Marrow Cells Biology Malignancy Article 03 medical and health sciences Mice 0302 clinical medicine hemic and lymphatic diseases Leukemia Myelogenous Chronic BCR-ABL Positive Genetics medicine Animals Molecular Biology neoplasms Mice Inbred BALB C Myeloid leukemia medicine.disease Hematopoietic Stem Cells Transplantation Leukemia Haematopoiesis 030104 developmental biology medicine.anatomical_structure Retroviridae 030220 oncology & carcinogenesis Cancer research Bone marrow Stem cell |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | Chronic myeloid leukemia (CML) is an age-dependent blood malignancy. Like many other age-dependent human diseases, laboratory animal research of CML uses young mice that do not factor in the influence of aging. To understand how aging may impact animal modeling of human age-dependent diseases, we established the first aging mouse model of human CML in BALB/c mice in the advanced age defined by 75% survival. This model was developed by noncytotoxic depletion of bone marrow lineage-positive cells followed by BCR-ABL retroviral transduction and transplantation. CML developed in aging mice shared many similarities to that in young mice, but had increased incidence of anemia that is often seen in human CML. Importantly, we showed that aging of both donor hematopoietic stem cells and recipient bone marrow niche impacted BCR-ABL mediated leukemogenesis and leukemia spectrum. Optimal CML induction relied on age-matching for donors and recipients, and cross-transplantation between young and old mice produced a mixture of different leukemia. Therefore, our model provides initial evidence of the feasibility and merit of CML modeling in aging mice and offers a new tool for future studies of CML stem cell drug resistance and therapeutic intervention in which aging would be taken into consideration as an influencing factor. |
| Databáze: | OpenAIRE |
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