Mutational analysis of therapy-related myelodysplastic syndromes and acute myelogenous leukemia | Aplastic Anemia and MDS International Foundation

Mutational analysis of therapy-related myelodysplastic syndromes and acute myelogenous leukemia

Journal Title: 
Haematologica
Author(s): 
Shih AH, Chung SS, Dolezal EK, Zhang SJ, Abdel-Wahab OI, Park CY, Nimer SD, Levine RL, Klimek VM
Primary Author: 
Shih AH
Original Publication Date: 
Thursday, January 24, 2013

Therapy-related myelodysplastic syndromes and acute myelogenous leukemia (t-MDS/AML) comprise a poor-risk subset of MDS/AML. Large scale mutation profiling efforts in de novo MDS have identified mutations that correlate with clinical features but such mutations have not been investigated in tMDS/AML. Genomic DNA from 38 patient samples was subjected to high throughput PCR and sequenced for TP53, TET2, DNMT3A, ASXL1, IDH1, IDH2, EZH2, EED, SUZ12, RBBP4, and splicing factors SRF2, U2AF35, and SF3B1. We identified somatic mutations in 16/38 (42%) patients. TP53 mutations were the most common lesion, detected in 8/38 (21%) patients, followed by TET2 in 4/38 (10.5%). Cases with a TP53 mutation or loss of the TP53 locus had a worse overall survival compared to those with wild type and intact TP53 (8.8 months vs 37.4 months p=.0035).

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