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.
Departments of Medicine, Mathematics and Statistics, State University of New York, Stony Brook, NY, USA. dgnatenko@notes.cc.sunysb.edu
Dmitri V
DV
Gnatenko
Wei
W
Zhu
Xiao
X
Xu
Edward T
ET
Samuel
Melissa
M
Monaghan
Mohammad H
MH
Zarrabi
Christi
C
Kim
Anil
A
Dhundale
Wadie F
WF
Bahou
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