Hematological malignancies (HM) are a heterogeneous group of life-threatening hematological diseases. The heterogeneity and clonal evolution of HM subpopulations are the main obstacles for precise diagnoses, risk stratification, and even targeted therapies. Standard bulk-sample genomic examinations average total mutations from multiple subpopulations and conceal the clonal diversity that may play a significant role in HM progression. Therefore, the development of novel methods that detect intra-tumor heterogeneity is critical for the discovery of novel potential therapeutic targets. The recently developed single cell sequencing (SCS) technologies can analyse genetic polymorphisms at a single cell level. SCS requires the precise isolation of single cells and amplification of their genetic material. It allows the analysis of genomic, transcriptomic, and epigenomic information in single cancer cells. SCS may also be able to monitor minimal residual disease (MRD) of HM by sequencing circulating tumor cells (CTCs) from peripheral blood. Functional heterogeneity and clonal evolution exist in acute leukemia, multiple myeloma (MM) and chronic myeloid leukemia (CML) subpopulations and have prognostic value. In this thesis, we provide an overview of SCS technologies in HM and discuss the heterogeneous genetic variation and clonal structure among subpopulations of HM. Furthermore, we aimed to shed light on the clinical applications of SCS technologies, including the development of new targeted therapies for drug-resistant or recurrent HM.
Keywords: Clonal evolution; Hematological malignancies; Heterogeneity; Precise therapy; Single cell sequencing.