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TP53 mutations predict decitabine-induced complete responses in patients with myelodysplastic syndromes.
- Source :
-
British Journal of Haematology . Feb2017, Vol. 176 Issue 4, p600-608. 9p. - Publication Year :
- 2017
-
Abstract
- To identify the molecular signatures that predict responses to decitabine ( DAC), we examined baseline gene mutations (28 target genes) in 109 myelodysplastic syndrome ( MDS) patients at diagnosis. We determined that TP53 mutations predicted complete response ( CR), as 10 of 15 patients (66·7%) who possessed TP53 mutations achieved a CR. Univariate and multivariate analyses showed that TP53 mutations are the only molecular signatures predictive of a CR to DAC in MDS. Among the ten patients with TP53 mutations who achieved a CR, nine presented with complex karyotypes due to abnormalities involving chromosome 5 and/or chromosome 7, and eight possessed monosomies. Although TP53 mutations were associated with a higher frequency of CRs, they were not associated with improved survival. Poor outcomes were attributed to early relapses and transformation to acute myeloid leukaemia after CR. Post- DAC therapy patient gene mutation profiles showed that most CR patients exhibited fewer gene mutations after achieving a CR. It seems that suppression of these gene mutations was facilitated by DAC, resulting in a CR. In summary, TP53 mutations might predict decitabine-induced complete responses in patients with MDS. DAC-induced responses may result from partial suppression of malignant clones containing mutated TP53 genes. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00071048
- Volume :
- 176
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- British Journal of Haematology
- Publication Type :
- Academic Journal
- Accession number :
- 121235444
- Full Text :
- https://doi.org/10.1111/bjh.14455