Class prediction models of thrombocytosis using genetic biomarkers
| Autor: | Dmitri V. Gnatenko, Wei Zhu, Wadie F. Bahou, Xiao Xu, Christi Kim, Melissa Monaghan, Anil Dhundale, Edward T. Samuel, Mohammad H. Zarrabi |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Genetic Markers Male Genotype Immunology Plenary Paper Biology Bioinformatics Biochemistry Cohort Studies medicine Humans Aged Oligonucleotide Array Sequence Analysis Thrombocytosis Sex Characteristics Models Genetic Microarray analysis techniques Essential thrombocythemia Gene Expression Profiling Discriminant Analysis Cell Biology Hematology Janus Kinase 2 Middle Aged Phlebotomy medicine.disease Gene expression profiling Genetic marker Biomarker (medicine) Female |
| Zdroj: | Blood. 115:7-14 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2009-05-224477 |
| Popis: | Criteria for distinguishing among etiologies of thrombocytosis are limited in their capacity to delineate clonal (essential thrombocythemia [ET]) from nonclonal (reactive thrombocytosis [RT]) etiologies. We studied platelet transcript profiles of 126 subjects (48 controls, 38 RT, 40 ET [24 contained the JAK2V617F mutation]) to identify transcript subsets that segregated phenotypes. Cross-platform consistency was validated using quantitative real-time polymerase chain reaction (RT-PCR). Class prediction algorithms were developed to assign phenotypic class between the thrombocytosis cohorts, and by JAK2 genotype. Sex differences were rare in normal and ET cohorts (< 1% of genes) but were male-skewed for approximately 3% of RT genes. An 11-biomarker gene subset using the microarray data discriminated among the 3 cohorts with 86.3% accuracy, with 93.6% accuracy in 2-way class prediction (ET vs RT). Subsequent quantitative RT-PCR analysis established that these biomarkers were 87.1% accurate in prospective classification of a new cohort. A 4-biomarker gene subset predicted JAK2 wild-type ET in more than 85% patient samples using either microarray or RT-PCR profiling, with lower predictive capacity in JAK2V617F mutant ET patients. These results establish that distinct genetic biomarker subsets can predict thrombocytosis class using routine phlebotomy. |
| Databáze: | OpenAIRE |
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