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Please use this identifier to cite or link to this item: http://hdl.handle.net/2108/1428

Title: Investigation on the mechanisms underlying the chromosomal translocations in therapy-related acute myeloid leukemias
Authors: Lo Coco, Francesco
Hasan, Syed Khizer
Keywords: acute promyelocytic leukemia
therapy related leukemia
non-homologous end joining
multiple sclerosis
Issue Date: 21-Aug-2010
Abstract: Therapy-related acute promyelocytic leukemia (t-APL) with the t(15;17) translocation is a well-recognized complication of cancer treatment with agents targeting topoisomerase II. However, cases are emerging following mitoxantrone therapy for multiple sclerosis (MS). Analysis of 12 cases of mitoxantrone-related t-APL in MS patients revealed an altered distribution of chromosome 15 breakpoints compared to de novo APL, biased towards disruption within PML intron 6 (11/12, 92% vs 622/1022, 61%: p=0.035). Despite this intron spanning ~1kb, the breakpoint in five mitoxantrone-treated patients fell within an 8bp region (1482-9) corresponding to the “hotspot” previously reported in t-APL complicating mitoxantrone-containing breast cancer therapy. Another shared breakpoint was identified within the ~17kb RARA intron 2 involving two t-APL cases arising after mitoxantrone treatment for MS and breast cancer, respectively. Analysis of PML and RARA genomic breakpoints in functional assays in 4 cas...
Description: 22. ciclo
URI: http://hdl.handle.net/2108/1428
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