The Potential Roles and Advantages of Single Cell Sequencing in the Diagnosis and Treatment of Hematological Malignancies

Abstract

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.

<p>Monitoring of Minimal Residual Disease (MRD) in Chronic Myeloid Leukemia: Recent Advances</p>

“…Single cell sequencing (SCS) technologies, based on single cells isolation and amplification of genetic material, have recently been developed. 125 It is now possible to analyse genomic, transcriptomic, and epigenomic information in single cancer cells, better defining the basis of clonal heterogeneity. SCS may also allow MRD monitoring in hematological malignancies by sequencing circulating tumor cells (CTCs) from PB.…”

Current perspectives on interethnic variability in multiple myeloma: Single cell technology, population pharmacogenetics and molecular signal transduction

“…Dissecting this cellular heterogeneity within the cancer milieu, especially in hematological malignancies such as MM, is a prerequisite for understanding the genesis of a cancer cell as a biological system, its homeostatic regulation and response to external perturbations [19] . Clonal evolution and functional heterogeneity are known to exist in MM subpopulations and are of prognostic significance [20] . Indeed, single cell sequencing technologies can facilitate the analysis of genetic polymorphisms at a single cell level [20] .…”

“…Clonal evolution and functional heterogeneity are known to exist in MM subpopulations and are of prognostic significance [20] . Indeed, single cell sequencing technologies can facilitate the analysis of genetic polymorphisms at a single cell level [20] . In an ideal clinical setting, single cell suspensions must be prepared immediately after sample collection from a patient.…”

Single-Cell Sequencing: Biological Insight and Potential Clinical Implications in Pediatric Leukemia

“…Not surprisingly, blood cancers are also among the entities most commonly analyzed in SCS studies, where generation of high-quality, single-cell suspensions is of key importance [ 24 , 25 ]. In line with this, leukemia samples as well as lymphoma cells circulating in the peripheral blood were the subjects in hematology-focused projects of early days [ 26 , 27 ], with acute myeloid leukemia (AML) being the most frequently published oncohematological entity [ 28 ]. To date, SCS datasets have been generated for a wide range of blood cancers, including chronic myeloid leukemia [ 29 ], myeloproliferative neoplasms [ 30 , 31 ], myelodysplastic syndrome/acute myeloid leukemia [ 21 , 27 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ], acute lymphoblastic leukemia (ALL) [ 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ], chronic lymphocytic leukemia [ 59 , 60 , 61 ], mantle cell lymphoma [ 61 , 62 , 63 ], follicular lymphoma [ 61 , 64 , 65 , …”

“…Several papers have recently been published on the status quo of single-cell technologies and on their applications in blood cancer research [ 20 , 21 , 22 , 24 , 25 , 28 , 74 , 75 , 76 ]. In this review, we specifically focus on pediatric leukemia with an aim to summarize how SCS studies shed light on the pathobiology of this disease group and discuss how different layers of single-cell omics approaches can expectedly support clinical decision making in the future.…”