Cargando…
IGF-IR determines the fates of BCR/ABL leukemia
BACKGROUND: The tyrosine kinase receptor insulin-like growth factor 1 receptor (IGF-IR) contributes to the initiation and progression of many types of malignancies. We previously showed that IGF-2, which binds IGF-IR, is an extrinsic factor that supports the ex vivo expansion of hematopoietic stem c...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320836/ https://www.ncbi.nlm.nih.gov/pubmed/25648584 http://dx.doi.org/10.1186/s13045-015-0106-8 |
_version_ | 1782356195599712256 |
---|---|
author | Xie, Jingjing Chen, Xiaoli Zheng, Junke Li, Chunling Stacy, Satomi Holzenberger, Martin Hu, Xuemei Zhang, Cheng Cheng |
author_facet | Xie, Jingjing Chen, Xiaoli Zheng, Junke Li, Chunling Stacy, Satomi Holzenberger, Martin Hu, Xuemei Zhang, Cheng Cheng |
author_sort | Xie, Jingjing |
collection | PubMed |
description | BACKGROUND: The tyrosine kinase receptor insulin-like growth factor 1 receptor (IGF-IR) contributes to the initiation and progression of many types of malignancies. We previously showed that IGF-2, which binds IGF-IR, is an extrinsic factor that supports the ex vivo expansion of hematopoietic stem cells (HSCs). We also demonstrated that IGF-IR is not required for HSC activity in vivo. METHODS AND RESULTS: Here we investigated the role of IGF-IR in chronic myeloid leukemia (CML) using the retroviral BCR/ABL transplantation mouse model. Existing antibodies against IGF-IR are not suitable for flow cytometry; therefore, we generated a fusion of the human IgG Fc fragment with mutant IGF-2 that can bind to IGF-IR. We used this fusion protein to evaluate mouse primary hematopoietic populations. Through transplantation assays with IGF-IR(+) and IGF-IR(−) cells, we demonstrated that IGF-IR is expressed on all mouse HSCs. The expression of IGF-IR is much higher on CML cells than on acute lymphoblastic leukemia (ALL) cells. The depletion of IGF-IR expression in BCR/ABL(+) cells led to the development of ALL (mostly T cell ALL) but not CML. Lack of IGF-IR resulted in decreased self-renewal of the BCR/ABL(+) CML cells in the serial replating assay. CONCLUSION: IGF-IR regulates the cell fate determination of BCR/ABL(+) leukemia cells and supports the self-renewal of CML cells. |
format | Online Article Text |
id | pubmed-4320836 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-43208362015-02-09 IGF-IR determines the fates of BCR/ABL leukemia Xie, Jingjing Chen, Xiaoli Zheng, Junke Li, Chunling Stacy, Satomi Holzenberger, Martin Hu, Xuemei Zhang, Cheng Cheng J Hematol Oncol Research BACKGROUND: The tyrosine kinase receptor insulin-like growth factor 1 receptor (IGF-IR) contributes to the initiation and progression of many types of malignancies. We previously showed that IGF-2, which binds IGF-IR, is an extrinsic factor that supports the ex vivo expansion of hematopoietic stem cells (HSCs). We also demonstrated that IGF-IR is not required for HSC activity in vivo. METHODS AND RESULTS: Here we investigated the role of IGF-IR in chronic myeloid leukemia (CML) using the retroviral BCR/ABL transplantation mouse model. Existing antibodies against IGF-IR are not suitable for flow cytometry; therefore, we generated a fusion of the human IgG Fc fragment with mutant IGF-2 that can bind to IGF-IR. We used this fusion protein to evaluate mouse primary hematopoietic populations. Through transplantation assays with IGF-IR(+) and IGF-IR(−) cells, we demonstrated that IGF-IR is expressed on all mouse HSCs. The expression of IGF-IR is much higher on CML cells than on acute lymphoblastic leukemia (ALL) cells. The depletion of IGF-IR expression in BCR/ABL(+) cells led to the development of ALL (mostly T cell ALL) but not CML. Lack of IGF-IR resulted in decreased self-renewal of the BCR/ABL(+) CML cells in the serial replating assay. CONCLUSION: IGF-IR regulates the cell fate determination of BCR/ABL(+) leukemia cells and supports the self-renewal of CML cells. BioMed Central 2015-02-04 /pmc/articles/PMC4320836/ /pubmed/25648584 http://dx.doi.org/10.1186/s13045-015-0106-8 Text en © Xie et al.; licensee Biomed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Xie, Jingjing Chen, Xiaoli Zheng, Junke Li, Chunling Stacy, Satomi Holzenberger, Martin Hu, Xuemei Zhang, Cheng Cheng IGF-IR determines the fates of BCR/ABL leukemia |
title | IGF-IR determines the fates of BCR/ABL leukemia |
title_full | IGF-IR determines the fates of BCR/ABL leukemia |
title_fullStr | IGF-IR determines the fates of BCR/ABL leukemia |
title_full_unstemmed | IGF-IR determines the fates of BCR/ABL leukemia |
title_short | IGF-IR determines the fates of BCR/ABL leukemia |
title_sort | igf-ir determines the fates of bcr/abl leukemia |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320836/ https://www.ncbi.nlm.nih.gov/pubmed/25648584 http://dx.doi.org/10.1186/s13045-015-0106-8 |
work_keys_str_mv | AT xiejingjing igfirdeterminesthefatesofbcrablleukemia AT chenxiaoli igfirdeterminesthefatesofbcrablleukemia AT zhengjunke igfirdeterminesthefatesofbcrablleukemia AT lichunling igfirdeterminesthefatesofbcrablleukemia AT stacysatomi igfirdeterminesthefatesofbcrablleukemia AT holzenbergermartin igfirdeterminesthefatesofbcrablleukemia AT huxuemei igfirdeterminesthefatesofbcrablleukemia AT zhangchengcheng igfirdeterminesthefatesofbcrablleukemia |