August 27, 2014
2 min read

Identification of 102 genes may help classify, treat patients with polycythemia vera

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Analysis of peripheral blood cells from patients with polycythemia vera identified 102 genes concordantly expressed in men and women that may help classify patients independently of their JAK2 V617F allele burden, according to study results.

These genes also may provide novel targets for therapy, researchers wrote.

Jerry L. Spivak, MD, director of the Center for Chronic Myeloproliferative Disorders at Johns Hopkins Medicine, and colleagues used oligonucleotide microarray technology to analyze the gene expression of CD34-positive peripheral blood cells from 19 patients with polycythemia vera.

Jerry L. Spivak, MD

Jerry L. Spivak

The analysis included eight men and 11 women. Median age (men, 71 years; women, 60 years) and disease duration (men, 12 years; women, 9 years) were comparable. All patients had JAK2 V617F expression.

Gene expression analyses indicated men had 571 genes that were differentially regulated, whereas women had 235 differentially regulated genes.

After excluding sex-specific gene expression, researchers identified 102 differentially expressed core genes — 68 which were up-regulated and 34 which were down-regulated — that were concordant between men and women.

Based on unsupervised hierarchical clustering of the 102 genes, researchers classified each patient’s disease as aggressive (n=7) or indolent (n=12). Age, neutrophil JAK2 V617F allele burden, white cell count, platelet count and clonal dominance were comparable between patients with aggressive and indolent disease.

Patients classified with aggressive disease had significantly longer median disease duration (14 years vs. 6 years; P=.05) and lower median hemoglobin levels (11.1 g/dL vs. 13.3 g/dL; P=.007). More patients with aggressive disease experienced thrombosis (4 vs. 1; P=.04), palpable splenomegaly (7 vs. 6; P=.03) or splenectomy (4 vs. 0; P=.007). They also were more likely to be exposed to chemotherapy (5 vs. 2; P=.03) or have disease that transformed to acute leukemia (4 vs. 1; P=.04). Eleven of 12 patients with indolent disease survived, compared with only one of the seven patients with aggressive disease (P=.001).

A supervised clustering approach based on top-scoring pairs identified 30 gene pairs — all of which were outside of the 102 core genes — used to classify disease as indolent or aggressive with 100% accuracy as the unsupervised approach.

“The data provides new insights into the genetic abnormalities of polycythemia vera, establish a molecular basis for disease heterogeneity, and identify genes and pathways that may have value for targeted therapy outside the canonical JAK2 signaling pathway, as well as previously unrecognized genes potentially involved in promoting myelofibrosis, inflammation and thrombosis,” Spivak and colleagues concluded. “The possibility that controlling for sex as a potential confounder is applicable to gene-expression analysis in other hematologic cancers warrants evaluation, given the insights described here.”

Disclosure: The study was funded in part by grants from the Department of Defense and the NIH. See the study for a full list of the researchers’ relevant financial disclosures.