Molecular heterogeneity and prognostic biomarkers in adults with acute myeloid leukemia and normal cytogenetics
Molecular heterogeneity and prognostic biomarkers in adults with acute myeloid leukemia and normal cytogenetics
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DOI：
10.1097/01.moh.0000149608.29685.d1
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发表时间：
2005-01-01
影响因子：
3.2
通讯作者：
Bloomfield, CD
中科院分区：
文献类型：
--
作者：
Marcucci, G;Mrózek, K;Bloomfield, CD
研究目的急性髓系白血病(AML)患者和核型正常的患者构成AML最大的单个细胞遗传学群体，估计占成人初治AML的45%。本文对这一组患者的分子异质性及其与预后分层和新的治疗方法的关系的最新文献进行了综述。最近的发现四种预后生物标记物--FLT3基因的内部串联复制和点突变、MLL基因的部分串联复制、CEBPA基因的突变和BAALC基因的过度表达--被发现可以预测细胞遗传学正常的AML患者的预后。此外，一项使用基因表达谱的研究发现，核型正常的AML患者的两个亚组的存活率存在显著差异。由于Flt3基因突变导致一种自磷酸化的、促进白血病发生的蛋白，一种新型酪氨酸激酶抑制剂的分子靶向治疗正在早期临床试验中探索。总结在细胞遗传学正常的AML患者的分子特征方面已经取得了可观的进展。未来的挑战是将这些生物学发现纳入新的风险适应治疗策略，以提高这类患者目前令人失望的治愈率(约25%-40%)。
Purpose of reviewPatients with acute myeloid leukemia (AML) and normal karyotype constitute the single largest cytogenetic group of AML, estimated to account for 45% of adults with de novo AML. This article critically reviews the recent literature that addresses the molecular heterogeneity of this group of patients and how this relates to prognostic stratification and novel therapeutic approaches.Recent findingsFour prognostic biomarkers-the internal tandem duplication and point mutations in the FLT3 gene, partial tandem duplication of the MLL gene, mutations of the CEBPA gene, and overexpression of the BAALC gene-have been found to predict outcome in patients with AML and normal cytogenetics. In addition, one study using gene expression profiling identified two subgroups of AML patients with a normal karyotype whose survival differs significantly. Because mutations in FLT3 result in an autophosphorylated, leukemogenesis-driving protein, molecular targeting therapy with a new class of tyrosine kinase inhibitors is being explores in early clinical trials.SummaryConsiderable progress has been made in molecular characterization of AML patients with normal cytogenetics. The challenge for the future is to incorporate these biologic discoveries into novel risk-adapted therapeutic strategies that will improve the currently disappointing cure rate (approximately 25-40%) of this group of patients.