Novel molecular and cellular therapeutic targets in acute lymphoblastic leukemia and lymphoproliferative disease.
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.
Brown
Valerie I
VI
Division of Oncology, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, ARC 902, 3615 Civic Center Boulevard, Philadelphia, PA, 19104, USA. brownv@email.chop.edu
Seif
Alix E
AE
Reid
Gregor S D
GS
Teachey
David T
DT
Grupp
Stephan A
SA
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008232:Lymphoproliferative Disorders / Q000378:metabolism / Q000628:therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism / Q000628:therapy*; D011494:Protein Kinases / Q000378:metabolism; D051881:Receptor, Notch1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases
D000276:Adjuvants, Immunologic; D004791:Enzyme Inhibitors; D051881:Receptor, Notch1; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases