Modeling of C/EBPalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells.
Mutations in the CEBPA gene are present in 7%-10% of human patients with acute myeloid leukemia (AML). However, no genetic models exist that demonstrate their etiological relevance. To mimic the most common mutations affecting CEBPA-that is, those leading to loss of the 42 kDa C/EBPalpha isoform (p4...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2008
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| _version_ | 1826296971129782272 |
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| author | Kirstetter, P Schuster, M Bereshchenko, O Moore, S Dvinge, H Kurz, E Theilgaard-Mönch, K Månsson, R Pedersen, T Pabst, T Schrock, E Porse, B Jacobsen, SE Bertone, P Tenen, D Nerlov, C |
| author_facet | Kirstetter, P Schuster, M Bereshchenko, O Moore, S Dvinge, H Kurz, E Theilgaard-Mönch, K Månsson, R Pedersen, T Pabst, T Schrock, E Porse, B Jacobsen, SE Bertone, P Tenen, D Nerlov, C |
| author_sort | Kirstetter, P |
| collection | OXFORD |
| description | Mutations in the CEBPA gene are present in 7%-10% of human patients with acute myeloid leukemia (AML). However, no genetic models exist that demonstrate their etiological relevance. To mimic the most common mutations affecting CEBPA-that is, those leading to loss of the 42 kDa C/EBPalpha isoform (p42) while retaining the 30kDa isoform (p30)-we modified the mouse Cebpa locus to express only p30. p30 supported the formation of granulocyte-macrophage progenitors. However, p42 was required for control of myeloid progenitor proliferation, and p42-deficient mice developed AML with complete penetrance. p42-deficient leukemia could be transferred by a Mac1+c-Kit+ population that gave rise only to myeloid cells in recipient mice. Expression profiling of this population against normal Mac1+c-Kit+ progenitors revealed a signature shared with MLL-AF9-transformed AML. |
| first_indexed | 2024-03-07T04:24:31Z |
| format | Journal article |
| id | oxford-uuid:cc29a621-241d-4392-a796-32dcf384ec2e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:24:31Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:cc29a621-241d-4392-a796-32dcf384ec2e2022-03-27T07:19:53ZModeling of C/EBPalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cc29a621-241d-4392-a796-32dcf384ec2eEnglishSymplectic Elements at Oxford2008Kirstetter, PSchuster, MBereshchenko, OMoore, SDvinge, HKurz, ETheilgaard-Mönch, KMånsson, RPedersen, TPabst, TSchrock, EPorse, BJacobsen, SEBertone, PTenen, DNerlov, CMutations in the CEBPA gene are present in 7%-10% of human patients with acute myeloid leukemia (AML). However, no genetic models exist that demonstrate their etiological relevance. To mimic the most common mutations affecting CEBPA-that is, those leading to loss of the 42 kDa C/EBPalpha isoform (p42) while retaining the 30kDa isoform (p30)-we modified the mouse Cebpa locus to express only p30. p30 supported the formation of granulocyte-macrophage progenitors. However, p42 was required for control of myeloid progenitor proliferation, and p42-deficient mice developed AML with complete penetrance. p42-deficient leukemia could be transferred by a Mac1+c-Kit+ population that gave rise only to myeloid cells in recipient mice. Expression profiling of this population against normal Mac1+c-Kit+ progenitors revealed a signature shared with MLL-AF9-transformed AML. |
| spellingShingle | Kirstetter, P Schuster, M Bereshchenko, O Moore, S Dvinge, H Kurz, E Theilgaard-Mönch, K Månsson, R Pedersen, T Pabst, T Schrock, E Porse, B Jacobsen, SE Bertone, P Tenen, D Nerlov, C Modeling of C/EBPalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells. |
| title | Modeling of C/EBPalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells. |
| title_full | Modeling of C/EBPalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells. |
| title_fullStr | Modeling of C/EBPalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells. |
| title_full_unstemmed | Modeling of C/EBPalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells. |
| title_short | Modeling of C/EBPalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells. |
| title_sort | modeling of c ebpalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia initiating cells |
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