Single-cell genomic profiling of acute myeloid leukemia for clinical use: A pilot study

Yan,Benedict; Hu,Yongli; Ban,Kenneth   H.K.; Tiang,Zenia; Ng,Christopher; Lee,Joanne; Tan,Wilson; Chiu,Lily; Tan,Tin  Wee; Seah,Elaine; Ng,Chin  Hin; Chng,Wee‑Joo; Foo,Roger

doi:10.3892/ol.2017.5669

Single-cell genomic profiling of acute myeloid leukemia for clinical use: A pilot study

Authors:
- Benedict Yan
- Yongli Hu
- Kenneth H.K. Ban
- Zenia Tiang
- Christopher Ng
- Joanne Lee
- Wilson Tan
- Lily Chiu
- Tin Wee Tan
- Elaine Seah
- Chin Hin Ng
- Wee‑Joo Chng
- Roger Foo
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Affiliations: Department of Laboratory Medicine, Molecular Diagnosis Centre, National University Health System, Singapore 119228, Republic of Singapore, Institute for Infocomm Research, Agency for Science, Technology and Research, Singapore 138632, Republic of Singapore, Department of Biochemistry, National University of Singapore, Singapore 117596, Republic of Singapore, Genome Institute of Singapore, Singapore 138672, Republic of Singapore, Department of Hematology‑Oncology, National University Cancer Institute, National University Health System, Singapore 119228, Republic of Singapore, National Supercomputing Centre, Singapore 138632, Republic of Singapore
Published online on: February 1, 2017 https://doi.org/10.3892/ol.2017.5669
Pages: 1625-1630
Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although bulk high-throughput genomic profiling studies have led to a significant increase in the understanding of cancer biology, there is increasing awareness that bulk profiling approaches do not completely elucidate tumor heterogeneity. Single-cell genomic profiling enables the distinction of tumor heterogeneity, and may improve clinical diagnosis through the identification and characterization of putative subclonal populations. In the present study, the challenges associated with a single‑cell genomics profiling workflow for clinical diagnostics were investigated. Single-cell RNA-sequencing (RNA‑seq) was performed on 20 cells from an acute myeloid leukemia bone marrow sample. Putative blasts were identified based on their gene expression profiles and principal component analysis was performed to identify outlier cells. Variant calling was performed on the single‑cell RNA‑seq data. The present pilot study demonstrates a proof of concept for clinical single‑cell genomic profiling. The recognized limitations include significant stochastic RNA loss and the relatively low throughput of the current proposed platform. Although the results of the present study are promising, further technological advances and protocol optimization are necessary for single‑cell genomic profiling to be clinically viable.

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