Impact of hemochromatosis gene mutations on cardiac status in doxorubicin-treated survivors of childhood high-risk leukemia.
Impact of hemochromatosis gene mutations on cardiac status in doxorubicin-treated survivors of childhood high-risk leukemia.
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DOI：
10.1002/cncr.28256
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发表时间：
2013-10-01
期刊：
影响因子：
6.2
通讯作者：
Silverman, Lewis B.
中科院分区：
文献类型：
--
作者：
Lipshultz, Steven E.;Lipsitz, Stuart R.;Kutok, Jeffery L.;Miller, Tracie L.;Colan, Steven D.;Neuberg, Donna S.;Stevenson, Kristen E.;Fleming, Mark D.;Sallan, Stephen E.;Franco, Vivian I.;Henkel, Jacqueline M.;Asselin, Barbara L.;Athale, Uma H.;Clavell, Luis A.;Michon, Bruno;Laverdiere, Caroline;Larsen, Eric;Kelly, Kara M.;Silverman, Lewis B.
阿霉素与进行性心功能障碍有关，可能是通过形成阿霉素-铁复合物导致自由基损伤。我们确定了与遗传性血色素沉着症相关的血色素沉着症（HFE）基因突变的频率，以及它们与儿童高风险急性淋巴细胞白血病幸存者阿霉素相关心脏毒性的关系。外周血检测两种常见的HFE等位基因变异：C282Y和H63D。在治疗期间检测血清心肌肌钙蛋白-t （cTnT）和n端前脑利钠肽（NT-proBNP），分别作为心脏损伤和心肌病的生物标志物。超声心动图评价左室结构和功能。184名患者的DNA结果至少有一种变异，167名患者两者都有：24%携带H63D， 10%携带C282Y。杂合子C282Y基因型与cTnT浓度的多次升高相关（p=0.039），但与NT-proBNP无关。在诊断后的中位2.2年（1.0-3.6），携带任何等位基因的儿童左室分数缩短（- 0.71 [0.25],p=0.008）、质量（- 0.84 [0.17],p<0.001）、收缩期末期（- 4.36 [0.26],p<0.001）和舒张末期后壁厚度（- 0.68 [0.25],p=0.01）的平均[SE] z评分均异常（n=32）。非携带者（n=63）的左室质量（- 0.45 [0.15],p=0.006）和收缩末期后壁厚度（- 4.06 [0.17],p<0.001）也低于正常水平。后来的随访显示了类似的结果。多柔比星相关心肌损伤与C282Y HFE携带者相关。尽管左室质量和壁厚总体上异常低，但在HFE携带者中，它们甚至更低，他们也有左室功能降低。筛查新诊断的癌症患者的HFE突变可以识别那些有多柔比星诱导的心脏毒性风险的患者。
Doxorubicin is associated with progressive cardiac dysfunction, possibly by forming doxorubicin-iron complexes leading to free-radical injury. We determined the frequency of hemochromatosis (HFE) gene mutations associated with hereditary hemochromatosis and their relationship with doxorubicin-associated cardiotoxicity in survivors of childhood high-risk acute lymphoblastic leukemia. Peripheral blood was tested for two common HFE allelic variants: C282Y and H63D. Serum cardiac troponin-T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP), biomarkers of cardiac injury and cardiomyopathy, respectively, were assayed during therapy. Left ventricular (LV) structure and function were assessed with echocardiography. 184 patients had DNA results for at least one variant, and 167 had both: 24% carried H63D and 10% carried C282Y. Heterozygous C282Y genotype was associated with multiple elevations in cTnT concentrations (p=0.039), but not NT-proBNP. At a median of 2.2 years (1.0–3.6) after diagnosis, mean [SE] Z-scores for LV fractional shortening (−0.71 [0.25], p=0.008), mass (−0.84 [0.17], p<0.001), and end-systolic (−4.36 [0.26], p<0.001) and end-diastolic posterior wall thickness (−0.68 [0.25], p=0.01) were abnormal in children with either allele (n=32). Non-carriers (n=63) also had below-normal LV mass (−0.45 [0.15], p=0.006) and end-systolic posterior wall thickness (−4.06 [0.17], p<0.001). Later follow-up showed similar results. Doxorubicin-associated myocardial injury was associated with C282Y HFE carriers. Although LV mass and wall thickness were abnormally low overall, they were even lower in HFE carriers, who also had reduced LV function. Screening newly-diagnosed cancer patients for HFE mutations may identify those at risk for doxorubicin-induced cardiotoxicity.
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影响因子：
4
作者：
Livesey, KJ;Wimhurst, VLC;Robson, KJH
通讯作者：
Robson, KJH
影响因子：
20.3
作者：
Miranda, CJ;Makui, H;Santos, MM
通讯作者：
Santos, MM
影响因子：
3.5
作者：
Cascales, Almudena;Sanchez-Vega, Beatriz;Ayala de la Pena, Francisco
通讯作者：
Ayala de la Pena, Francisco
DOI：
10.1007/bf01976756
发表时间：
1993-09-01
期刊：
AGENTS AND ACTIONS
影响因子：
--
作者：
BUSS, JL;HASINOFF, BB
通讯作者：
HASINOFF, BB
影响因子：
51.1
作者：
Lipshultz, Steven E.;Scully, Rebecca E.;Lipsitz, Stuart R.;Sallan, Stephen E.;Silverman, Lewis B.;Miller, Tracie L.;Borry, Elly V.;Asselin, Barbara L.;Athale, Uma;Clavell, Luis A.;Larsen, Eric;Moghrabi, Albert;Samson, Yvan;Michon, Bruno;Schorin, Marshall A.;Cohen, Harvey J.;Neuberg, Donna S.;Orav, E. John;Colan, Steven D.
通讯作者：
Colan, Steven D.