TY - JOUR
T1 - Identification of genes associated with chemotherapy crossresistance and treatment response in childhood acute lymphoblastic leukemia
AU - Lugthart, Sanne
AU - Cheok, Meyling H
AU - den Boer, Monique L
AU - Yang, Wenjian
AU - Holleman, Amy
AU - Cheng, Cheng
AU - Pui, Ching-Hon
AU - Relling, Mary V
AU - Janka-Schaub, Gritta E
AU - Pieters, Rob
AU - Evans, William E
N1 - Funding Information:
This work was supported in part by the following grants: the Junior research fellowship of the Sophia Children’s Hospital Foundation and the Dutch Cancer Foundation 2003, the Netherlands (S.L.); the Pediatric Oncology Foundation and the Nijbakker-Morra Foundation, the Netherlands (M.L.d.B., A.H.); the Renee Vogel Stipendium 2002, the Netherlands (A.H.); the National Institutes of Health, RO1 CA51001 (M.V.R., C.-H.P.); the National Institutes of Health, U01 GM61393 (M.V.R., W.E.E.); the National Institutes of Health, R37 CA36401, R01 CA78224, U01 GM61393, and U01 GM61374 and the American Lebanese Syrian Associated Charities (M.V.R., C.-H.P., W.E.E.); Cancer Center Support Grant P30 CA21765 and the American Cancer Society and F.M. Kirby Clinical Research Professorship (C.-H.P.). The authors gratefully acknowledge the outstanding technical support of all technicians involved at the Research Laboratories at Erasmus MC/Sophia Children’s Hospital and at St. Jude Children’s Research Hospital. We also thank Deqing Pei, Michael Shipman, Dr. Suraj Mukatira, and Dr. Clayton Naeve and his staff in the Hartwell Center for Bioinformatics and Biotechnology at St. Jude. We are indebted to all clinical staff at St. Jude, Erasmus MC/Sophia and the COALL centers of all who cared for these patients and to the patients and parents for their participation in these studies.
PY - 2005/4
Y1 - 2005/4
N2 - Acute lymphoblastic leukemia (ALL) can be cured with combination chemotherapy in over 75% of children, but the cause of treatment failure in the remaining patients is unknown. We determined the sensitivity of ALL cells to individual antileukemic agents in 441 patients and used a genome-wide approach to identify 45 genes differentially expressed in ALL exhibiting crossresistance to prednisolone, vincristine, asparaginase, and daunorubicin. We also identified a distinct phenotype of discordant resistance to asparaginase and vincristine and 139 genes whose expression was associated with this novel phenotype. The expression of these genes discriminated treatment outcome in two independent patient populations, identifying a subset of patients with a markedly inferior outcome (37% +/- 13% 5 year DFS).
AB - Acute lymphoblastic leukemia (ALL) can be cured with combination chemotherapy in over 75% of children, but the cause of treatment failure in the remaining patients is unknown. We determined the sensitivity of ALL cells to individual antileukemic agents in 441 patients and used a genome-wide approach to identify 45 genes differentially expressed in ALL exhibiting crossresistance to prednisolone, vincristine, asparaginase, and daunorubicin. We also identified a distinct phenotype of discordant resistance to asparaginase and vincristine and 139 genes whose expression was associated with this novel phenotype. The expression of these genes discriminated treatment outcome in two independent patient populations, identifying a subset of patients with a markedly inferior outcome (37% +/- 13% 5 year DFS).
KW - Age Factors
KW - Antineoplastic Agents/pharmacology
KW - Asparaginase/pharmacology
KW - Cell Survival/drug effects
KW - Child
KW - Cluster Analysis
KW - Core Binding Factor Alpha 2 Subunit
KW - Daunorubicin/pharmacology
KW - Disease-Free Survival
KW - Drug Resistance, Multiple/genetics
KW - Drug Resistance, Neoplasm/genetics
KW - Gene Expression Profiling
KW - Gene Expression Regulation, Neoplastic/drug effects
KW - Homeodomain Proteins/genetics
KW - Humans
KW - Mercaptopurine/pharmacology
KW - Neoplasm Recurrence, Local
KW - Oncogene Proteins, Fusion/genetics
KW - Phenotype
KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
KW - Predictive Value of Tests
KW - Prednisolone/pharmacology
KW - Principal Component Analysis
KW - Proportional Hazards Models
KW - Translocation, Genetic/genetics
KW - Treatment Outcome
KW - Tumor Cells, Cultured
KW - Vincristine/pharmacology
UR - http://www.scopus.com/inward/record.url?scp=20244377046&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2005.03.002
DO - 10.1016/j.ccr.2005.03.002
M3 - Article
C2 - 15837626
SN - 1535-6108
VL - 7
SP - 375
EP - 386
JO - Cancer cell
JF - Cancer cell
IS - 4
ER -