title: Gene expression-based classification and regulatory networks of pediatric acute lymphoblastic leukemia.
abstract: Pediatric acute lymphoblastic leukemia (ALL) contains cytogenetically distinct subtypes that respond differently to cytotoxic drugs. Subtype classification can be also achieved through gene expression profiling. However, how to apply such classifiers to a single patient and correctly diagnose the disease subtype in an independent patient group has not been addressed. Furthermore, the underlying regulatory mechanisms responsible for the subtype-specific gene expression patterns are still largely unknown. Here, by combining 3 published microarray datasets on 535 mostly white children's samples and generating a new dataset on 100 Chinese children's ALL samples, we were able to (1) identify a 62-gene classifier with 97.6% accuracy from the white children's samples and validated it on the completely independent set of 100 Chinese samples, and (2) uncover potential regulatory networks of ALL subtypes. The classifier we identified was, thus far, the only one that could be applied directly to a single sample and that sustained validation in a large independent patient group. Our results also suggest that the etiology of ALL is largely the same among different ethnic groups, and that the transcription factor hubs in the predicted regulatory network might play important roles in regulating gene expression and development of ALL.
authors.affiliation: Beijing Children's Hospital of Capital Medical University, Beijing, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Minyuan
authors.initials: M
authors.lastname: Wu
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhu
authors.forename: Chao
authors.initials: C
authors.lastname: Gao
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.forename: Ruidong
authors.initials: R
authors.lastname: Zhang
authors.forename: Nan
authors.initials: N
authors.lastname: Qiao
authors.forename: Huiling
authors.initials: H
authors.lastname: Xue
authors.forename: Yamei
authors.initials: Y
authors.lastname: Hu
authors.forename: Shilai
authors.initials: S
authors.lastname: Bao
authors.forename: Huyong
authors.initials: H
authors.lastname: Zheng
authors.forename: Jing-Dong J
authors.initials: JD
authors.lastname: Han
mesh_terms: D002648:Child; D057225:Data Mining; D030541:Databases, Genetic; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000145:classification* / Q000235:genetics*; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction