Hoxa9 collaborates with E2A-PBX1 in mouse B cell leukemia in association with Flt3 activation and decrease of B cell gene expression
Background: The fusion protein E2A-PBX1 induces pediatric B cell leukemia in human. Previously, we reported oncogenic interactions between homeobox (Hox) genes and E2A-PBX1 in murine T cell leukemia. A proviral insertional mutagenesis screen with our E2A-PBX1 B cell leukemia mouse model identified H...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
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Wiley
2014
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| Online Access: | https://eprints.nottingham.ac.uk/42822/ |
| _version_ | 1848796576735035392 |
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| author | Hassawi, Mona Shestakova, Elena A. Fournier, Marilaine Lebert-Ghali, Charles-Étienne Vaisson, Gratianne Frison, Héloïse Sinnett, Daniel Vidal, Ramon Thompson, Alexander Bijl, Janet J. |
| author_facet | Hassawi, Mona Shestakova, Elena A. Fournier, Marilaine Lebert-Ghali, Charles-Étienne Vaisson, Gratianne Frison, Héloïse Sinnett, Daniel Vidal, Ramon Thompson, Alexander Bijl, Janet J. |
| author_sort | Hassawi, Mona |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Background: The fusion protein E2A-PBX1 induces pediatric B cell leukemia in human. Previously, we reported oncogenic interactions between homeobox (Hox) genes and E2A-PBX1 in murine T cell leukemia. A proviral insertional mutagenesis screen with our E2A-PBX1 B cell leukemia mouse model identified Hoxa genes as potential collaborators to E2A-PBX1. Here we studied whether Hoxa9 could enhance E2A-PBX1 leukemogenesis. Results: We show that Hoxa9 confers a proliferative advantage to E2A-PBX1 B cells. Transplantation experiments with E2A-PBX1 transgenic B cells overexpressing Hoxa9 isolated from bone marrow chimeras showed that Hoxa9 accelerates the generation of E2A-PBX1 B cell leukemia, but Hoxa9 is unable to transform B cells alone. Quantitative-reverse transcriptase polymerase chain reaction analysis demonstrated a strong repression of B cell specific genes in these E2A-PBX1/Hoxa9 leukemias in addition to Flt3 activation, indicating inhibition of B cell differentiation in combination with enhanced proliferation. Overexpression of Hoxa9 in established E2A-PBX1 mouse leukemic B cells resulted in a growth advantage in vitro, which was also characterized by an enhanced expression of Flt3. Conclusions: we show for the first time that Hoxa9 collaborates with E2A-PBX1 in the oncogenic transformation of B cells in a mouse model that involves Flt3 signaling, which is potentially relevant to human disease. |
| first_indexed | 2025-11-14T19:50:11Z |
| format | Article |
| id | nottingham-42822 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:50:11Z |
| publishDate | 2014 |
| publisher | Wiley |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-428222020-05-04T20:15:44Z https://eprints.nottingham.ac.uk/42822/ Hoxa9 collaborates with E2A-PBX1 in mouse B cell leukemia in association with Flt3 activation and decrease of B cell gene expression Hassawi, Mona Shestakova, Elena A. Fournier, Marilaine Lebert-Ghali, Charles-Étienne Vaisson, Gratianne Frison, Héloïse Sinnett, Daniel Vidal, Ramon Thompson, Alexander Bijl, Janet J. Background: The fusion protein E2A-PBX1 induces pediatric B cell leukemia in human. Previously, we reported oncogenic interactions between homeobox (Hox) genes and E2A-PBX1 in murine T cell leukemia. A proviral insertional mutagenesis screen with our E2A-PBX1 B cell leukemia mouse model identified Hoxa genes as potential collaborators to E2A-PBX1. Here we studied whether Hoxa9 could enhance E2A-PBX1 leukemogenesis. Results: We show that Hoxa9 confers a proliferative advantage to E2A-PBX1 B cells. Transplantation experiments with E2A-PBX1 transgenic B cells overexpressing Hoxa9 isolated from bone marrow chimeras showed that Hoxa9 accelerates the generation of E2A-PBX1 B cell leukemia, but Hoxa9 is unable to transform B cells alone. Quantitative-reverse transcriptase polymerase chain reaction analysis demonstrated a strong repression of B cell specific genes in these E2A-PBX1/Hoxa9 leukemias in addition to Flt3 activation, indicating inhibition of B cell differentiation in combination with enhanced proliferation. Overexpression of Hoxa9 in established E2A-PBX1 mouse leukemic B cells resulted in a growth advantage in vitro, which was also characterized by an enhanced expression of Flt3. Conclusions: we show for the first time that Hoxa9 collaborates with E2A-PBX1 in the oncogenic transformation of B cells in a mouse model that involves Flt3 signaling, which is potentially relevant to human disease. Wiley 2014-01 Article PeerReviewed Hassawi, Mona, Shestakova, Elena A., Fournier, Marilaine, Lebert-Ghali, Charles-Étienne, Vaisson, Gratianne, Frison, Héloïse, Sinnett, Daniel, Vidal, Ramon, Thompson, Alexander and Bijl, Janet J. (2014) Hoxa9 collaborates with E2A-PBX1 in mouse B cell leukemia in association with Flt3 activation and decrease of B cell gene expression. Developmental Dynamics, 243 (1). pp. 145-158. ISSN 1097-0177 Hox genes; oncogenes; transgenic mouse model; transcription factors http://onlinelibrary.wiley.com/doi/10.1002/dvdy.24056/abstract doi:10.1002/dvdy.24056 doi:10.1002/dvdy.24056 |
| spellingShingle | Hox genes; oncogenes; transgenic mouse model; transcription factors Hassawi, Mona Shestakova, Elena A. Fournier, Marilaine Lebert-Ghali, Charles-Étienne Vaisson, Gratianne Frison, Héloïse Sinnett, Daniel Vidal, Ramon Thompson, Alexander Bijl, Janet J. Hoxa9 collaborates with E2A-PBX1 in mouse B cell leukemia in association with Flt3 activation and decrease of B cell gene expression |
| title | Hoxa9 collaborates with E2A-PBX1 in mouse B cell leukemia in association with Flt3 activation and decrease of B cell gene expression |
| title_full | Hoxa9 collaborates with E2A-PBX1 in mouse B cell leukemia in association with Flt3 activation and decrease of B cell gene expression |
| title_fullStr | Hoxa9 collaborates with E2A-PBX1 in mouse B cell leukemia in association with Flt3 activation and decrease of B cell gene expression |
| title_full_unstemmed | Hoxa9 collaborates with E2A-PBX1 in mouse B cell leukemia in association with Flt3 activation and decrease of B cell gene expression |
| title_short | Hoxa9 collaborates with E2A-PBX1 in mouse B cell leukemia in association with Flt3 activation and decrease of B cell gene expression |
| title_sort | hoxa9 collaborates with e2a-pbx1 in mouse b cell leukemia in association with flt3 activation and decrease of b cell gene expression |
| topic | Hox genes; oncogenes; transgenic mouse model; transcription factors |
| url | https://eprints.nottingham.ac.uk/42822/ https://eprints.nottingham.ac.uk/42822/ https://eprints.nottingham.ac.uk/42822/ |