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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Fri, Jul 25, 2008 at 11:44 PM
Subject: Molecular analysis of t(15;17) genomic breakpoints in secondary acute promyelocytic leukemia arising after treatment of multiple sclerosis.
To: mesothelioma77@gmail.com
[1]Blood. 2008 Jul 23;
Hasan SK, Mays AN, Ottone T, Ledda A, La Nasa G, Cattaneo C, Borlenghi E, Melillo L, Montefusco E, Cervera J, Stephen C, Satchi G, Lennard A, Libura M, Byl JA, Osheroff N, Amadori S, Felix CA, Voso MT, Sperr WR, Esteve J, Sanz MA, Grimwade D, Lo-Coco F
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 approximately 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 approximately 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 cases, including the shared RARA intron 2 breakpoint at 14446-49, confirmed each to be preferential sites of topoisomerase IIalpha-mediated DNA cleavage in the presence of mitoxantrone. This study further supports the presence of preferential sites of DNA damage induced by mitoxantrone in PML and RARA genes that may underlie the propensity to develop this particular subtype of leukemia following exposure to this agent.
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Source: http://www.hubmed.org/display.cgi?uids=18650449
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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Fri, Jul 25, 2008 at 11:44 PM
Subject: Molecular analysis of t(15;17) genomic breakpoints in secondary acute promyelocytic leukemia arising after treatment of multiple sclerosis.
To: mesothelioma77@gmail.com
[1]Blood. 2008 Jul 23;
Hasan SK, Mays AN, Ottone T, Ledda A, La Nasa G, Cattaneo C, Borlenghi E, Melillo L, Montefusco E, Cervera J, Stephen C, Satchi G, Lennard A, Libura M, Byl JA, Osheroff N, Amadori S, Felix CA, Voso MT, Sperr WR, Esteve J, Sanz MA, Grimwade D, Lo-Coco F
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 approximately 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 approximately 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 cases, including the shared RARA intron 2 breakpoint at 14446-49, confirmed each to be preferential sites of topoisomerase IIalpha-mediated DNA cleavage in the presence of mitoxantrone. This study further supports the presence of preferential sites of DNA damage induced by mitoxantrone in PML and RARA genes that may underlie the propensity to develop this particular subtype of leukemia following exposure to this agent.
___
Source: http://www.hubmed.org/display.cgi?uids=18650449
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