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Mutational spectrum of myeloid malignancies with inv(3)/t(3;3) reveals a predominant involvement of RAS/RTK signaling pathways.
- Source :
-
Blood . 1/1/2015, Vol. 125 Issue 1, p133-139. 7p. - Publication Year :
- 2015
-
Abstract
- 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, chronic myeloid leukemia, and myelodysplastic syndrome cases, suggesting recognition of 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00064971
- Volume :
- 125
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 100264519
- Full Text :
- https://doi.org/10.1182/blood-2014-07-591461