Yanagisawa Breann, Ghiaur Gabriel, Smith B Douglas, Jones Richard J
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Exp Hematol. 2016 Dec;44(12):1130-1137. doi: 10.1016/j.exphem.2016.08.010. Epub 2016 Sep 28.
Considerable evidence suggests that rare leukemia cells with stem cell features, including self-renewal capacity and drug resistance, are primarily responsible for both disease maintenance and relapses. Traditionally, these so-called leukemia stem cells (LSCs) have been identified in the laboratory by their ability to engraft acute myeloid leukemia (AML) into immunocompromised mice. For many years, only those rare AML cells characterized by a hematopoietic stem cell (HSC) CD34CD38 phenotype were believed capable of generating leukemia in immunocompromised mice. However, more recently, significant heterogeneity in the phenotypes of those AML cells that can engraft immunocompromised mice has been demonstrated. AML cells that engraft immunocompromised mice have also been shown to not necessarily represent either the founder clone or those cells responsible for relapse. A recent study found that the most immature phenotype present in an AML correlated with genetically defined risk groups and outcomes, but was heterogeneous. Patients with AML cells expressing a primitive HSC phenotype (CD34CD38 with high aldehyde dehydrogenase activity) manifested significantly lower complete remission rates, as well as poorer event-free and overall survivals. Leukemias in which the most primitive cells displayed more mature phenotypes were associated with better outcomes. The strong clinical correlations suggest that the most immature phenotype detectable within a patient's AML might serve as a biomarker for "clinically relevant" LSCs.
大量证据表明，具有干细胞特征（包括自我更新能力和耐药性）的罕见白血病细胞是疾病维持和复发的主要原因。传统上，这些所谓的白血病干细胞（LSC）在实验室中是通过它们将急性髓系白血病（AML）植入免疫缺陷小鼠体内的能力来鉴定的。多年来，人们一直认为只有那些具有造血干细胞（HSC）CD34CD38表型的罕见AML细胞才能在免疫缺陷小鼠中引发白血病。然而，最近已证明能够植入免疫缺陷小鼠体内的AML细胞的表型存在显著异质性。能够植入免疫缺陷小鼠体内的AML细胞也不一定代表起始克隆或那些导致复发的细胞。最近一项研究发现，AML中存在的最不成熟表型与基因定义的风险组和预后相关，但具有异质性。表达原始HSC表型（CD34CD38且醛脱氢酶活性高）的AML患者的完全缓解率显著较低，无事件生存期和总生存期也较差。最原始细胞表现出更成熟表型的白血病与更好的预后相关。强烈的临床相关性表明，患者AML中可检测到的最不成熟表型可能作为“临床相关”LSC的生物标志物。
