TY - JOUR
T1 - Novel molecular and cellular therapeutic targets in acute lymphoblastic leukemia and lymphoproliferative disease
AU - Brown, Valerie I.
AU - Seif, Alix E.
AU - Reid, Gregor S.D.
AU - Teachey, David T.
AU - Grupp, Stephan A.
N1 - Funding Information:
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).
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=61849157793&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=61849157793&partnerID=8YFLogxK
U2 - 10.1007/s12026-008-8038-9
DO - 10.1007/s12026-008-8038-9
M3 - Review article
C2 - 18716718
AN - SCOPUS:61849157793
SN - 0257-277X
VL - 42
SP - 84
EP - 105
JO - Immunologic Research
JF - Immunologic Research
IS - 1-3
ER -