Altinoz Meric A, Elmaci Ilhan, Bolukbasi Fatih Han, Ekmekci Cumhur Gokhan, Yenmis Guven, Sari Ramazan, Sav Aydin
a Neuroacademy Group , Istanbul , Turkey.
b Department of Neurosurgery , Memorial Hospital , Istanbul , Turkey.
J Chemother. 2017 Aug;29(4):238-244. doi: 10.1080/1120009X.2017.1312752. Epub 2017 Apr 23.
Temozolomide may cause thrombocytopenia or neutropenia in 3-4% of glioblastoma patients, respectively. However, pancytopenia is rarely reported. MGMT (O6-methylguanine-DNA-methyltransferase) enzyme repairs temozolomide-induced DNA mutations and associates both with antitumour efficacy and myelosuppression. Many studies on the effects of MGMT gene-methylation on temozolomide's effects exist, but much fewer publications concerning MGMT variants were documented. A full sequencing of the MGMT gene was performed in a female glioblastoma patient, who developed pancytopenia following temozolomide treatment. Results indicated the presence of all the rs2308321 (I143 V), rs2308327 (K178R) and rs12917 (L84F) MGMT-variants, which were previously associated with temozolomide myelotoxicity. rs12917 (L84F) variant was reported as associating with lesser risk of gallbladder tumours, yet with higher risk of non-Hodgkin lymphomas related with exposure to chlorinated solvents or hair dyes. DNA repair proteins may exert diverging effects on DNA injuries caused by different chemicals and therefore exerting complex effects on myelotoxicity, antitumour activity and carcinogenesis.
替莫唑胺可能分别导致3%-4%的胶质母细胞瘤患者出现血小板减少或中性粒细胞减少。然而，全血细胞减少的报道很少。MGMT（O6-甲基鸟嘌呤-DNA甲基转移酶）可修复替莫唑胺诱导的DNA突变，并且与抗肿瘤疗效和骨髓抑制均相关。关于MGMT基因甲基化对替莫唑胺作用影响的研究很多，但关于MGMT变异体的文献则少得多。对一名女性胶质母细胞瘤患者进行了MGMT基因的全序列分析，该患者在接受替莫唑胺治疗后出现了全血细胞减少。结果表明存在所有rs2308321（I143V）、rs2308327（K178R）和rs12917（L84F）MGMT变异体，这些变异体先前与替莫唑胺的骨髓毒性有关。rs12917（L84F）变异体被报道与胆囊肿瘤风险较低相关，但与接触氯化溶剂或染发剂相关的非霍奇金淋巴瘤风险较高相关。DNA修复蛋白可能对不同化学物质引起的DNA损伤产生不同影响，因此对骨髓毒性、抗肿瘤活性和致癌作用产生复杂影响。
