Department of Medical & Molecular Genetics, King's College London School of Medicine, London, United Kingdom.
Hematology Am Soc Hematol Educ Program. 2009:385-95. doi: 10.1182/asheducation-2009.1.385.
Over the last three decades there have been dramatic advances in deciphering the cytogenetic and molecular lesions underlying the pathogenesis of acute myeloid leukemia (AML). These have not only afforded greater insights into disease biology, but also provided useful information predicting the likelihood of any given patient achieving and maintaining remission following conventional chemotherapy, leading to the development of risk-stratified treatment approaches. However, it is becoming increasingly apparent that AML is highly heterogeneous at the molecular level. Defining the individual genetic abnormalities or combinations of markers that provide significant independent prognostic information and establishing their respective relationships to other pre-treatment characteristics that impact on outcome, such as age and presenting white blood cell count, presents a major ongoing challenge. Moreover, there is increasing evidence that risk of relapse and overall survival can be predicted by assessment of kinetics and depth of response following front-line therapy and monitoring of the leukemic burden using molecular or immunological approaches to minimal residual disease (MRD) detection. These advances present the exciting prospect that panels of pre-treatment parameters affording independent prognostic information can be integrated with precise measurement of treatment response using MRD technologies to provide greater refinement in risk-adapted management of AML. This could lead to further improvements in outcome and serve to identify in a more reliable fashion those patients most likely to benefit from allogeneic transplant in first remission.
在过去的三十年中，人们在解析急性髓系白血病（AML）发病机制的细胞遗传学和分子病变方面取得了巨大进展。这些不仅使人们对疾病生物学有了更深入的了解，还提供了有关预测任何特定患者在接受常规化疗后实现并维持缓解的可能性的有用信息，从而导致了风险分层治疗方法的发展。然而，AML 在分子水平上高度异质性这一点变得越来越明显。确定提供重要独立预后信息的个体遗传异常或标记物组合，并确定它们与其他影响结果的治疗前特征（如年龄和白细胞计数）的各自关系，是一个重大的挑战。此外，越来越多的证据表明，可以通过评估一线治疗后的动力学和反应深度以及使用分子或免疫方法检测微小残留病（MRD）来监测白血病负担，来预测复发风险和总生存。这些进展为我们带来了令人兴奋的前景，即能够提供独立预后信息的预处理参数组合可以与使用 MRD 技术精确测量治疗反应相结合，从而在 AML 的风险适应管理方面提供更高的细化。这可能会进一步改善预后，并以更可靠的方式确定那些最有可能从缓解期异基因移植中受益的患者。
