Liquori Alessandro, Ibañez Mariam, Sargas Claudia, Sanz Miguel Ángel, Barragán Eva, Cervera José
Accredited Research Group in Hematology and Hemotherapy, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain.
Department of Hematology, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain.
Cancers (Basel). 2020 Mar 8;12(3):624. doi: 10.3390/cancers12030624.
Although acute promyelocytic leukemia (APL) is one of the most characterized forms of acute myeloid leukemia (AML), the molecular mechanisms involved in the development and progression of this disease are still a matter of study. APL is defined by the rearrangement as a consequence of the translocation t(15;17)(q24;q21). However, this abnormality alone is not able to trigger the whole leukemic phenotype and secondary cooperating events might contribute to APL pathogenesis. Additional somatic mutations are known to occur recurrently in several genes, such as , , and , whereas mutations in other common AML genes are rarely detected, resulting in a different molecular profile compared to other AML subtypes. How this mutational spectrum, including point mutations in the fusion gene, could contribute to the 10%-15% of relapsed or resistant APL patients is still unknown. Moreover, due to the uncertain impact of additional mutations on prognosis, the identification of the APL-specific genetic lesion is still the only method recommended in the routine evaluation/screening at diagnosis and for minimal residual disease (MRD) assessment. However, the gene expression profile of genes, such as , and once combined with the molecular events, might improve future prognostic models, allowing us to predict clinical outcomes and to categorize APL patients in different risk subsets, as recently reported. In this review, we will focus on the molecular characterization of APL patients at diagnosis, relapse and resistance, in both children and adults. We will also describe different standardized molecular approaches to study MRD, including those recently developed. Finally, we will discuss how novel molecular findings can improve the management of this disease.
尽管急性早幼粒细胞白血病（APL）是急性髓系白血病（AML）中特征最为明确的类型之一，但该疾病发生和发展所涉及的分子机制仍有待研究。APL是由t(15;17)(q24;q21)易位导致的重排所定义。然而，仅这种异常并不能引发整个白血病表型，继发性协同事件可能有助于APL的发病机制。已知其他体细胞突变会在多个基因中反复出现，如 、 、 和 ，而在其他常见AML基因中的突变很少被检测到，这导致与其他AML亚型相比分子谱不同。包括融合基因点突变在内的这种突变谱如何导致10%-15%的复发或耐药APL患者仍不清楚。此外，由于其他突变对预后的影响不确定，在诊断时的常规评估/筛查以及微小残留病（MRD）评估中，鉴定APL特异性遗传病变仍然是唯一推荐的方法。然而，如 、 和 等基因的基因表达谱一旦与分子事件相结合，可能会改善未来的预后模型，使我们能够预测临床结果并将APL患者分类到不同的风险亚组中，正如最近报道的那样。在这篇综述中，我们将重点关注儿童和成人APL患者在诊断、复发和耐药时的分子特征。我们还将描述研究MRD的不同标准化分子方法，包括最近开发的方法。最后，我们将讨论新的分子发现如何改善这种疾病的管理。
