Print Friendly, PDF & Email

Essential thrombocythemia

New research suggests genomic characteristics of patients with myeloproliferative neoplasms (MPNs) can predict clinical outcomes.

Investigators defined eight genomic subgroups of MPNs, each with distinct clinical features, including event-free survival, risk of leukemic transformation, and blood counts.

Jacob Grinfeld, MD, of the University of Cambridge in the U.K., and his colleagues described these findings in The New England Journal of Medicine.

This study included 2,035 patients with MPNs, including essential thrombocythemia, polycythemia vera, myelofibrosis, and other diagnoses.

The investigators performed targeted sequencing for the full coding sequence of 69 genes and genome-wide copy number information in 1,887 patients. Whole-exome sequencing was performed in another 148 patients.

By sequencing coding exons from 69 myeloid cancer genes, the investigators were able to survey the diversity of mutations across MPN patients and identify mutation-associated clinical outcomes.

The results showed that slightly less than half (45%) of the patients had a solitary abnormality in CALR, MPL, or JAK2, while the remaining patients had additional driver mutations.

In some instances, additional mutations were numerous, particularly in older patients with advanced disease. In at least five cases, 33 genes had driver mutations.

Further analysis revealed eight genomic subgroups that could predict clinical outcomes based on shared chromosomal abnormalities and mutations.

For example, one subgroup included patients with TP53 mutations. These individuals had a “dismal prognosis” and were 15.5 times more likely to transform to acute myeloid leukemia, compared with the JAK2-heterozygous subgroup (P<0.001).

Because prognosis is “a key determinant” of MPN treatment, genomic subgrouping may one day guide clinical decision-making, the investigators concluded.

To further this cause, they have made available an online calculator of individualized patient outcomes, which can be accessed at

This study was funded by the Wellcome Trust, the National Institute for Health Research Cambridge Biomedical Research Centre, Cancer Research UK, and others. Some study authors reported fees from Celgene, Novartis, Gilead, Shire, and others outside of the study.

Print Friendly, PDF & Email