Abstract:
Acute myeloid leukemia (AML) is characterized by impaired differentiation and indefinite proliferation of abnormal myeloid progenitors. Although differentiating agents were deemed to revolutionize AML therapy, most treated non-APL AML patients are refractory or relapse. According to cancer stem cell model, leukemia-initiating cells are the root cause of relapse given their unidirectional potential to generate differentiated AML blasts. Nonetheless, accumulating evidences emphasize the de-differentiation plasticity and leukemogenic potential of mature AML blasts and the frailty of targeting leukemic stem cells per se. This review critically discusses the potential and challenges of (lessons learnt from) conventional and novel differentiating agents in AML therapy. Although differentiating agents might hold promise, they should be exploited within the context of a rationale combination regimen eradicating all maturation/differentiation states of AML cells. The results of the routinely used immunophenotypic markers and/or morphological analyses of differentiation should be carefully interpreted given their propensity to underestimate AML burden.
摘要:
急性髓性白血病(AML)的特征是异常髓样祖细胞的分化受损和无限增殖。尽管区分剂被认为是AML治疗的革命性变化,大多数接受治疗的非APLAML患者难治或复发.根据癌症干细胞模型,白血病起始细胞是复发的根本原因,因为它们具有产生分化的AML母细胞的单向潜力。尽管如此,越来越多的证据强调成熟AML母细胞的去分化可塑性和白血病发生潜力,以及靶向白血病干细胞本身的弱点.这篇综述批判性地讨论了AML治疗中常规和新型分化药物的潜力和挑战(从中学到的教训)。尽管区分代理人可能有希望,应在消除AML细胞所有成熟/分化状态的原理组合方案的背景下加以利用.常规使用的免疫表型标记和/或分化形态学分析的结果应仔细解释,因为它们倾向于低估AML负担。