Structural and functional analysis of the cytidine deaminase gene in patients with acute myeloid leukaemia
Structural and functional analysis of the cytidine deaminase gene in patients with acute myeloid leukaemia
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DOI：
10.1046/j.1365-2141.1998.01084.x
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发表时间：
1998-12-01
影响因子：
6.5
通讯作者：
Schütte, J
中科院分区：
文献类型：
--
作者：
Schröder, JK;Kirch, C;Schütte, J
胞苷脱氨酶(CDD)基因转移在体外可诱导细胞对阿糖胞苷(AraC)产生耐药性。为了探讨CDD在急性髓系白血病(AML)中的作用，我们分析了初治和难治AML患者原始细胞中CDD活性和CDD基因结构。初治AML患者的CDD活性中位数显著低于RF-AML原始细胞(P=0.015)，诱导化疗后完全缓解患者的CDD活性显著低于原始细胞持续患者(P=0.043)。通过Southern分析和RT-PCR对CDD基因的结构进行了研究，没有发现可检测到的异常。对9例RF-AML患者的CDD基因进行了序列分析，发现3例患者的CDD基因发生了不一致的变异。CDD mRNA表达的半定量评估显示：与CDD活性显著相关。总而言之，与最近的另一项研究一致，我们的数据表明治疗前CDD活性与诱导治疗反应之间存在相关性。除了先前描述的MDR1表达对预后的影响外，这一结果可能有助于开发适合风险的AML治疗策略，并为进一步研究明确的AML患者队列中的CDD活性以及参与CDD活性调节的机制提供依据。
Gene transfer of the cytidine deaminase (CDD) cDNA has recently been shown to induce cellular resistance to cytarabine (AraC) in vitro. To investigate the role for CDD in acute myeloid leukaemia (AML) we analysed the CDD activity and CDD gene structure in blast material from well-defined patients with untreated and AraC refractory (RF) AML. Median CDD activity in previously untreated AML was significantly lower than in RF-AML blasts (P=0.015) and was significantly lower in patients with complete remission than with blast persistence following induction chemotherapy (P=0.043). Structural investigation of the CDD gene by Southern analyses and RT-PCR showed no detectable aberrations. Sequence analysis of the CDD cDNA from nine RF-AML patients showed inconsistent aberrations in three patients. Semiquantitative assessment of CDD mRNA expression revealed a significant: correlation with CDD activity. In conclusion concordant with another recent study our data suggest a correlation of pretherapeutic CDD activity with induction treatment response. Besides the previously described prognostic impact of mdr1 expression, this result could be useful for the development of risk-adapted AML treatment strategies and warrants further studies of CDD activity in well-defined cohorts of AML patients and of the mechanisms involved in the regulation of CDD activity.