Long-term Imatinib Treatment does not Cause Testicular Toxicity in Male Adolescents with Chronic Myeloid Leukemia and in a Juvenile Rat Model
Long-term Imatinib Treatment does not Cause Testicular Toxicity in Male Adolescents with Chronic Myeloid Leukemia and in a Juvenile Rat Model
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长期伊马替尼治疗不会导致患有慢性粒细胞白血病的男性青少年和幼年大鼠模型的睾丸毒性
DOI：
10.1055/s-0034-1372643
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Suttorp M
中科院分区：
文献类型：
--
作者：
Tauer JT;Ulmer A;Glauche I;Jung R;Suttorp M
背景：暴露于酪氨酸激酶抑制剂伊马替尼（IMA）对男性生殖内分泌系统的影响仍有争议。因此，我们研究了长期TKI治疗的慢性髓性白血病（CML）男性青少年血清睾酮（Testo）和抑制素B （InB）。此外，在幼年大鼠模型中研究了长期暴露于TKIs的情况。方法：对13例接受TKI治疗3 - 58个月（中位18个月）的CML患儿（年龄7.8-18.9岁，中位12.8岁），每隔3个月采集血清。将4周龄雄性大鼠长期或间歇性地通过饮用水暴露于标准（SD）和高剂量（=2倍SD）的IMA、达沙替尼（DASA）或博舒替尼（BOSU），持续10 w。控制组只接收水。动物在暴露2 w（青春期前）、4 w（青春期）和10 w（青春期后）后处死。ELISA法检测血清Testo和InB水平。结果：男孩的Testo和InB水平在正常的年龄相关参考范围内，TKI治疗期间没有观察到水平上升或下降的模式。在大鼠中，与对照组相比，IMA暴露组的Testo水平在青春期后趋于不显著降低，而DASA和BOSU暴露组的Testo水平无显著差异。在所有TKIs的所有剂量和所有应用方案测试中，动物的InB水平与对照组没有显着差异。结论：由于测试个体数量较少，TKI引起的睾丸毒性似乎不太可能，因为无论是在男性青少年患者还是长期暴露于TKI的大鼠中，都没有观察到Testo和InB血液水平的改变。
Background:The impact of exposure to the tyrosine kinase inhibitor (TKI) imatinib (IMA) on the male reproductive endocrine system is still discussed controversially. We therefore investigated testosterone (Testo) and inhibin B (InB) in blood serum from male adolescents with chronic myeloid leukemia (CML) under long-term TKI treatment. Also long-term exposure to TKIs was studied in a juvenile rat model.Methods:Serum was collected at 3 months intervals from 13 boys (age: 7.8–18.9 years, median: 12.8 years) with CML receiving TKI treatment over 3–58 months (median: 18 months). 4 weeks (w) old male rats were exposed, either chronically or intermittently, via the drinking water to a standard (SD) and a high dose (=2-fold SD) of IMA, dasatinib (DASA), or bosutinib (BOSU) over a 10 w period. Controls received water only. Animals were sacrificed after 2 w (prepubertal), 4 w (pubertal), and 10 w (postpubertal) of exposure. Testo and InB serum levels were measured by ELISA.Results:Boys exhibited Testo and InB levels within normal age-related reference ranges and no pattern of rising or falling levels during TKI treatment could be observed. In rats, Testo levels under IMA exposure tended to be non-significantly lowered at postpubertal age compared to controls while no significant differences were found under DASA and BOSU exposure. Animals’ InB levels did not significantly differ from controls for all TKIs, at all doses, and by all application schemes tested.Conclusion:With the limitation that the number of individuals tested was rather small, testicular toxicity due to TKI seems unlikely as no alterations of Testo and InB blood levels neither in male adolescent patients nor in rats under long-term TKI exposure was observed.
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TK 抑制剂治疗扰乱生长激素轴：慢性粒细胞白血病儿童的临床观察和幼年动物模型的实验数据
DOI：
--
发表时间：
2013
期刊：
Klinische Pädiatrie
影响因子：
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作者：
A. Ulmer;J. Tauer;I. Glauche;Roland Jung;M. Suttorp
通讯作者：
M. Suttorp
影响因子：
3.6
作者：
Hensley, ML;Ford, JM
通讯作者：
Ford, JM
影响因子：
--
作者：
Nurmio, Mirja;Toppari, Jorma;Jahnukainen, Kirsi
通讯作者：
Jahnukainen, Kirsi
伊马替尼不会损害性腺功能。
DOI：
--
发表时间：
2012
期刊：
Leukemia research : a Forum for Studies on Leukemia and Normal Hemopoiesis
影响因子：
--
作者：
C. Chuah
通讯作者：
C. Chuah
非受体酪氨酸激酶抑制剂 (TKI) 的非选择性副作用
DOI：
--
发表时间：
2011
期刊：
影响因子：
--
作者：
J. Tauer;L. Hofbauer;S. König;M. Suttorp
通讯作者：
M. Suttorp