Identification of genes associated with chemotherapy crossresistance and treatment response in childhood acute lymphoblastic leukemia

Sanne Lugthart, Meyling H Cheok, Monique L den Boer, Wenjian Yang, Amy Holleman, Cheng Cheng, Ching-Hon Pui, Mary V Relling, Gritta E Janka-Schaub, Rob Pieters, William E Evans

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

Samenvatting

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).

Originele taal-2Engels
Pagina's (van-tot)375-86
Aantal pagina's12
TijdschriftCancer cell
Volume7
Nummer van het tijdschrift4
DOI's
StatusGepubliceerd - apr. 2005
Extern gepubliceerdJa

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