Mutational spectrum of myeloid malignancies with inv(3)/t(3;3) reveals a predominant involvement of RAS/RTK signaling pathways
Myeloid malignancies bearing chromosomal inv(3)/t(3;3) abnormalities are among the most therapy-resistant leukemias. Deregulated expression of EVI1 is the molecular hallmark of this disease; however, the genome-wide spectrum of cooperating mutations in this disease subset has not been systematically...
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| Main Author: | |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2015
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| In: |
Blood
Year: 2015, Volume: 125, Issue: 1, Pages: 133-139 |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood-2014-07-591461 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1182/blood-2014-07-591461
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| Author Notes: | Stefan Gröschel, Mathijs A. Sanders, Remco Hoogenboezem, Annelieke Zeilemaker, Marije Havermans, Claudia Erpelinck, Eric M. J. Bindels, H. Berna Beverloo, Hartmut Döhner, Bob Löwenberg, Konstanze Döhner, Ruud Delwel, and Peter J. M. Valk |
| Summary: | Myeloid malignancies bearing chromosomal inv(3)/t(3;3) abnormalities are among the most therapy-resistant leukemias. Deregulated expression of EVI1 is the molecular hallmark of this disease; however, the genome-wide spectrum of cooperating mutations in this disease subset has not been systematically elucidated. Here, we show that 98% of inv(3)/t(3;3) myeloid malignancies harbor mutations in genes activating RAS/receptor tyrosine kinase (RTK) signaling pathways. In addition, hemizygous mutations in GATA2, as well as heterozygous alterations in RUNX1, SF3B1, and genes encoding epigenetic modifiers, frequently co-occur with the inv(3)/t(3;3) aberration. Notably, neither mutational patterns nor gene expression profiles differ across inv(3)/t(3;3) acute myeloid leukemia, chronicmyeloid leukemia, and myelodysplastic syndromecases, suggesting recognitionof inv(3)/t(3;3) myeloid malignancies as a single disease entity irrespective of blast count. The high incidence of activating RAS/RTK signaling mutations may provide a target for a rational treatment strategy in this high-risk patient group. |
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| Item Description: | Gesehen am 11.01.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood-2014-07-591461 |