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- Title
Genome-wide approach to identify risk factors for therapy-related myeloid leukemia.
- Authors
Bogni, A.; Cheng, C.; Liu, W.; Yang, W.; Pfeffer, J.; Mukatira, S.; French, D.; Downing, J. R.; Pui, C-H; Relling, M. V.
- Abstract
Using a target gene approach, only a few host genetic risk factors for treatment-related myeloid leukemia (t-ML) have been defined. Gene expression microarrays allow for a more genome-wide approach to assess possible genetic risk factors for t-ML. We assessed gene expression profiles (n=12 625 probe sets) in diagnostic acute lymphoblastic leukemic cells from 228 children treated on protocols that included leukemogenic agents such as etoposide, 13 of whom developed t-ML. Expression of 68 probes, corresponding to 63 genes, was significantly related to risk of t-ML. Hierarchical clustering of these probe sets clustered patients into three groups with 94, 122 and 12 patients, respectively; 12 of the 13 patients who went on to develop t-ML were overrepresented in the latter group (P<0.0001). A permutation test indicated a low likelihood that these probe sets and clusters were obtained by chance (P<0.001). Distinguishing genes included transcription-related oncogenes (v-Myb, Pax-5), cyclins (CCNG1, CCNG2 and CCND1) and histone HIST1H4C. Common transcription factor recognition elements among similarly up- or downregulated genes included several involved in hematopoietic differentiation or leukemogenesis (Maz, PU.1, ARNT). This approach has identified several genes whose expression distinguishes patients at risk of t-ML, and suggests targets for assessing germline predisposition to leukemogenesis.Leukemia (2006) 20, 239–246. doi:10.1038/sj.leu.2404059; published online 8 December 2005
- Subjects
MYELOID leukemia; BONE marrow diseases; BLOOD diseases; DISEASE risk factors; GENE targeting; GENOMES; MEDICAL genetics
- Publication
Leukemia (08876924), 2006, Vol 20, Issue 2, p239
- ISSN
0887-6924
- Publication type
Article
- DOI
10.1038/sj.leu.2404059