Immunology and Molecular Oncology Unit, Veneto Institute of Oncology, IOV-IRCCS, 35128 Padova, Italy.
Onco Hematology, Department of Oncology, Veneto Institute of Oncology, IOV-IRCCS, 31033 Padua, Italy.
Int J Mol Sci. 2023 Oct 18;24(20):15325. doi: 10.3390/ijms242015325.
The molecular basis of Down syndrome (DS) predisposition to leukemia is not fully understood but involves various factors such as chromosomal abnormalities, oncogenic mutations, epigenetic alterations, and changes in selection dynamics. Myeloid leukemia associated with DS (ML-DS) is preceded by a preleukemic phase called transient abnormal myelopoiesis driven by gene mutations and progresses to ML-DS via additional mutations in cohesin genes, , , or pathway genes. DS-related ALL (ALL-DS) differs from non-DS ALL in terms of cytogenetic subgroups and genetic driver events, and the aberrant expression of , mutations, and pathway-activating mutations are frequent in ALL-DS. Recent advancements in single-cell multi-omics technologies have provided unprecedented insights into the cellular and molecular heterogeneity of DS-associated hematologic neoplasms. Single-cell RNA sequencing and digital spatial profiling enable the identification of rare cell subpopulations, characterization of clonal evolution dynamics, and exploration of the tumor microenvironment's role. These approaches may help identify new druggable targets and tailor therapeutic interventions based on distinct molecular profiles, ultimately improving patient outcomes with the potential to guide personalized medicine approaches and the development of targeted therapies.
唐氏综合征（DS）易患白血病的分子基础尚未完全阐明，但涉及多种因素，如染色体异常、致癌突变、表观遗传改变和选择动力学变化。与 DS 相关的髓性白血病（ML-DS）之前存在一个称为短暂性髓系前白血病的前期阶段，由基因突变驱动，通过黏合蛋白基因、、、或通路基因的额外突变进展为 ML-DS。DS 相关的急性淋巴细胞白血病（ALL-DS）在细胞遗传学亚组和遗传驱动事件方面与非 DS ALL 不同，并且 ALL-DS 中经常出现、突变和通路激活突变的异常表达。单细胞多组学技术的最新进展为 DS 相关血液肿瘤的细胞和分子异质性提供了前所未有的见解。单细胞 RNA 测序和数字空间分析能够鉴定稀有细胞亚群、描述克隆进化动力学以及探索肿瘤微环境的作用。这些方法可能有助于确定新的可药物治疗靶点，并根据不同的分子谱进行治疗干预，最终提高患者的治疗效果，有可能指导个体化医学方法和靶向治疗的发展。
