Class prediction models of thrombocytosis using genetic biomarkers.
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 JAK2V(617)F 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 JAK2V(617)F mutant ET patients. These results establish that distinct genetic biomarker subsets can predict thrombocytosis class using routine phlebotomy.
Gnatenko
Dmitri V
DV
Departments of Medicine, Mathematics and Statistics, State University of New York, Stony Brook, NY, USA. dgnatenko@notes.cc.sunysb.edu
Zhu
Wei
W
Xu
Xiao
X
Samuel
Edward T
ET
Monaghan
Melissa
M
Zarrabi
Mohammad H
MH
Kim
Christi
C
Dhundale
Anil
A
Bahou
Wadie F
WF
D000328:Adult; D000368:Aged; D015331:Cohort Studies; D016002:Discriminant Analysis; D005260:Female; D020869:Gene Expression Profiling; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D012727:Sex Characteristics; D013922:Thrombocytosis / Q000145:classification* / Q000201:enzymology / Q000235:genetics*
D005819:Genetic Markers; D053614:Janus Kinase 2