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Addressing heterogeneity of individual blood cancers: the need for single cell analysis

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Abstract

Cancer heterogeneity is a significant factor in response to treatment and escape leading to relapse. Within an individual cancer, especially blood cancers, there exists multiple subclones as well as distinct clonal expansions unrelated to the clinically detected, dominant clone. Over time, multiple subclones and clones undergo emergence, expansion, and extinction. Although sometimes this intra-clonal and inter-clonal heterogeneity can be detected and/or quantified in tests that measure aggregate populations of cells, frequently, such heterogeneity can only be detected using single cell analysis to determine its frequency and to detect minor clones that may subsequently emerge to become drug resistant and dominant. Most genetic/genomic tests look at the pooled tumor population as a whole rather than at its individual cellular components. Yet, minor clones and cancer stem cells are unlikely to be detected against the background of expanded major clones. Because selective pressures are likely to govern much of what is seen clinically, single cell analysis allows identification of otherwise cryptic compartments of the malignancy that may ultimately mediate progression and relapse. Single cell analysis can track intra- or inter-clonal heterogeneity and provide useful clinical information, often before changes in the disease are detectable in the clinic. To a very limited extent, single cell analysis has already found roles in clinical care. Because inter- and intra-clonal heterogeneity likely occurs more frequently than can be currently appreciated on a clinical level, future use of single cell analysis is likely to have profound clinical utility.

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Abbreviations

ALL:

acute lymphocytic leukemia

CLL:

chronic lymphocytic leukemia

CTC:

circulating tumor cells

EGFR:

epidermal growth factor receptor

FISH:

fluorescence in situ hybridization

IgH:

immunoglobulin heavy chain

MBCL:

monoclonal B-cell lymphocytosis

MM:

multiple myeloma

MRD:

minimal residual disease

PCR:

polymerase chain reaction

TKI:

tyrosine kinase inhibitor

WM:

Waldenstrom macroglobulinemia

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Acknowledgments

We are grateful for the research support provided by the Myeloma Alberta Support Society, and thank the patients who so generously donate samples of their tissue.

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Authors and Affiliations

  1. Department of Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue NW, Edmonton, AB, T6G 1Z2, Canada

    Michael P. Chu, Jitra Kriangkum, Christopher P. Venner, Irwindeep Sandhu, Joanne Hewitt, Andrew R. Belch & Linda M. Pilarski

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  1. Michael P. Chu
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  2. Jitra Kriangkum
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  3. Christopher P. Venner
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  4. Irwindeep Sandhu
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  7. Linda M. Pilarski
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Correspondence to Michael P. Chu.

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Chu, M.P., Kriangkum, J., Venner, C.P. et al. Addressing heterogeneity of individual blood cancers: the need for single cell analysis. Cell Biol Toxicol 33, 83–97 (2017). https://doi.org/10.1007/s10565-016-9367-4

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