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Application of Next-Generation Sequencing-Based Mutational Profiling in Acute Lymphoblastic Leukemia

  • Acute Lymphocytic Leukemias (M Keng and F El Chaer, Section Editors)
  • Published:
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Abstract

Purpose of Review

Recent efforts to characterize hematologic cancers with genetic and molecular detail have largely relied on mutational profiling via next-generation sequencing (NGS). The application of NGS-guided disease prognostication and clinical decision making requires a basic understanding of sequencing advantages, pitfalls, and areas where clinical care might be enhanced by the knowledge generated. This article identifies avenues within the landscape of adult acute lymphoblastic leukemia (ALL) where mutational data hold the opportunity to enhance understanding of disease biology and patient care.

Recent Findings

NGS-based assessment of measurable residual disease (MRD) after ALL treatment allows for a sensitive and specific molecular survey that is at least comparable, if not superior, to existing techniques. Mutational assessment by NGS has unraveled complex signaling networks that drive pathogenesis of T-cell ALL. Sequencing of patients with familial clustering of ALL has also identified novel germline mutations whose inheritance predisposes to disease development in successive generations.

Summary

While NGS-based assessment of hematopoietic malignancies often provides actionable information to clinicians, patients with acute lymphoblastic leukemia are left underserved due to a lack of disease classification and prognostication schema that integrate molecular data. Ongoing research is positioned to enrich the molecular toolbox available to clinicians caring for adult ALL patients and deliver new insights to guide therapeutic selection, monitor clinical response, and detect relapse.

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  1. Ahmed Aleem, and Ali R. Haque contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine, Loyola University Medical Center, 2160 S. 1st Ave, Maywood, IL, 60153, USA

    Ahmed Aleem, Ali R. Haque & Gregory W. Roloff

  2. Leukemia Service, Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA

    Elizabeth A. Griffiths

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G.W.R. and E.A.G conceived and designed the article. A.A., A.R.H, and G.W.R. performed the primary literature review. All authors contributed to the writing of the manuscript. All authors approve of the final manuscript and are accountable for the work.

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Correspondence to Gregory W. Roloff.

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Dr. Griffiths has received honoraria/advisory board payments from Alexion Pharmaceuticals, Celgene/BMS, AbbVie, and Novartis. EAG has also received institutional research funding from Genentech Inc., Appelis pharmaceuticals, Celldex Therapeutics, and Celgene/BMS. The other authors declare no conflicts of interest/competing interests.

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Aleem, A., Haque, A.R., Roloff, G.W. et al. Application of Next-Generation Sequencing-Based Mutational Profiling in Acute Lymphoblastic Leukemia. Curr Hematol Malig Rep 16, 394–404 (2021). https://doi.org/10.1007/s11899-021-00641-5

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