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Characteristics and Therapeutic Targeting of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia

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Biological Mechanisms of Minimal Residual Disease and Systemic Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1100))

Abstract

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Early response to therapy, especially the measurement of minimal residual disease (MRD), remains the most reliable and strongest independent prognostic parameter. Intriguingly, little is known on the mechanisms sustaining MRD in that disease. Here, we summarize existing evidence on the influences of molecular genetics and clonal architecture of childhood ALL on disease persistence. Also, the impact of the leukemic niche on residual leukemia cells in the bone marrow and extramedullary compartments is reviewed. We further discuss existing in vivo models of minimal residual disease based on different cellular labelling strategies and engraftment of ALL cells in immunodeficient mouse strains. We finally draw some conclusions on potential strategies targeting residual ALL cells, with a focus on cellular and antibody-based immunotherapy.

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Acknowledgement

IJ was funded by ERC Consolidator Grant 681524; Mildred Scheel Professorship by German Cancer Aid; German Research Foundation (DFG), Collaborative Research Center 1243 “Genetic and epigenetic evolution of hematopoietic neoplasms”, project A05; DFG proposal MA 1876/13-1; and by Bettina Bräu Stiftung and Dr. Helmut Legerlotz Stiftung. DS was funded by a Max Eder Fellowship by the German Cancer Aid, the Wilhelm-Sander-Stiftung and the Deutsche José-Carreras Leukämiestiftung.

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Authors and Affiliations

  1. Research Unit Apoptosis in Hematopoietic Stem Cells, Helmholtz Center Munich, German Center for Environmental Health (HMGU), Munich, Germany

    Irmela Jeremias

  2. Department of Pediatrics, Dr. von Hauner Childrens Hospital, Ludwig Maximilians University, Munich, Germany

    Irmela Jeremias

  3. German Consortium for Translational Cancer Research (DKTK), Partnering Site Munich, Munich, Germany

    Irmela Jeremias

  4. Department of Pediatrics I, Pediatric Hematology/Oncology, ALL-BFM Study Group, University Hospital Schleswig-Holstein, Kiel, Germany

    Denis M. Schewe

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  1. Irmela Jeremias
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Correspondence to Denis M. Schewe .

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  1. Division of Hematology and Oncology, Department of Medicine, Department of Otolaryngology, Department of Oncological Sciences, Tisch Cancer Institute, Black Family Stem Cell Institute, Mount Sinai School of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Julio A. Aguirre-Ghiso

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Jeremias, I., Schewe, D.M. (2018). Characteristics and Therapeutic Targeting of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia. In: Aguirre-Ghiso, J. (eds) Biological Mechanisms of Minimal Residual Disease and Systemic Cancer. Advances in Experimental Medicine and Biology, vol 1100. Springer, Cham. https://doi.org/10.1007/978-3-319-97746-1_8

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