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Novel molecular and cellular therapeutic targets in acute lymphoblastic leukemia and lymphoproliferative disease

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Abstract

While the outcome for pediatric patients with lymphoproliferative disorders (LPD) or lymphoid malignancies, such as acute lymphoblastic leukemia (ALL), has improved dramatically, patients often suffer from therapeutic sequelae. Additionally, despite intensified treatment, the prognosis remains dismal for patients with refractory or relapsed disease. Thus, novel biologically targeted treatment approaches are needed. These targets can be identified by understanding how a loss of lymphocyte homeostasis can result in LPD or ALL. Herein, we review potential molecular and cellular therapeutic strategies that (i) target key signaling networks (e.g., PI3K/AKT/mTOR, JAK/STAT, Notch1, and SRC kinase family-containing pathways) which regulate lymphocyte growth, survival, and function; (ii) block the interaction of ALL cells with stromal cells or lymphoid growth factors secreted by the bone marrow microenvironment; or (iii) stimulate innate and adaptive immune responses.

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Acknowledgments

This article was supported by grants NIH 1 K08 CA104882-01A1, grant # IRG-78-002-30 from the American Cancer Society, the Children’s Cancer Fund, and the Florence R.C. Murray Program at the Children’s Hospital of Philadelphia (VIB); the WW Smith Charitable Trust (VIB and SAG); NIH CA102646, CA1116660, ACS RSG0507101, and the Sanford Chair and Weinberg Funds of the Children’s Hospital of Philadelphia (SAG), ASCO Young Investigator and Career Development Awards, and the Larry and Helen Hoag Foundation Clinical Translational Research Career Development Award (DTT); NIH R03 CA123554, Foerderer-Murray Program at the Children’s Hospital of Philadelphia (GSDR).

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  1. Division of Oncology, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, ARC 902, 3615 Civic Center Boulevard, Philadelphia, PA, 19104, USA

    Valerie I. Brown, Alix E. Seif, Gregor S. D. Reid, David T. Teachey & Stephan A. Grupp

  2. Division of Hematology, Department of Pediatrics, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA, 19104, USA

    David T. Teachey

  3. Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA, 19104, USA

    Stephan A. Grupp

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  1. Valerie I. Brown
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Correspondence to Valerie I. Brown.

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Brown, V.I., Seif, A.E., Reid, G.S.D. et al. Novel molecular and cellular therapeutic targets in acute lymphoblastic leukemia and lymphoproliferative disease. Immunol Res 42, 84–105 (2008). https://doi.org/10.1007/s12026-008-8038-9

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