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Leukemia’s Clonal Evolution in Development, Progression, and Relapse

  • Jui Wan Loh
  • Hossein KhiabanianEmail author
Mathematical Models of Stem Cell Behavior (M Kohandel, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Mathematical Models of Stem Cell Behavior

Abstract

Purpose of Review

Advances in high-throughput methods have enabled the molecular characterization of leukemias and have improved our understanding of their clonal evolution from leukemogenesis in hematopoietic stem/progenitor cells to overt diagnosable disease.

Recent Findings

It has now been revealed that during leukemia’s development and progression, genetic alterations accumulate according to the principles of Darwinian evolution. Drug resistance often emerges from changes in evolutionary trajectories of disease through selection of subpopulations that have greater fitness under therapy. In this manuscript, we will review recent data on prevalence of highly branched evolutionary patterns in myeloid and lymphoid leukemias and discuss how different treatment strategies differentially shape leukemia’s clonal architecture.

Summary

Increasing evidence on clinical impact of small pre-malignant clones prior to diagnosis and small resistant clones during treatment strongly suggests that highly sensitive experimental and mathematical models are necessary for accurate dissection of hematopoietic populations and robust identification of predictive markers for disease transformation and relapse.

Keywords

Leukemia Clonal evolution Hematopoietic stem cells Leukemogenesis Pre-malignant cells Tumor dynamics 

Notes

Acknowledgments

J-WL is a pre-doctoral fellow of the New Jersey Commission on Cancer Research (DFS18PPC017). HK acknowledges support from Rutgers Cancer Institute of New Jersey (P30CA072720).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Authors and Affiliations

  1. 1.Rutgers Cancer Institute of New JerseyRutgers UniversityNew BrunswickUSA
  2. 2.Center for Systems and Computational Biology, Rutgers Cancer Institute of New JerseyRutgers UniversityNew BrunswickUSA
  3. 3.Graduate Program in Microbiology and Molecular GeneticsRutgers UniversityPiscatawayUSA
  4. 4.Department of Pathology and Laboratory Medicine, Rutgers Robert Wood Johnson Medical SchoolRutgers UniversityNew BrunswickUSA

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