Published in

National Academy of Sciences, Proceedings of the National Academy of Sciences, 42(111), p. 15190-15195, 2014

DOI: 10.1073/pnas.1401873111

Links

Tools

Export citation

Search in Google Scholar

JAK2V617F promotes replication fork stalling with disease-restricted impairment of the intra-S checkpoint response

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

Full text: Download

Red circle
Preprint: archiving forbidden
Green circle
Postprint: archiving allowed
Red circle
Published version: archiving forbidden
Data provided by SHERPA/RoMEO

Abstract

Significance Cancers arise through a succession of enabling genetic lesions, but the consequences of many driver mutations remain unclear, especially in the earliest stages of tumor formation. The myeloproliferative neoplasms (MPNs) encompass a group of chronic hematologic disorders that can collectively provide a window into these early stages of leukemia evolution. This study reveals a role for the JAK2V617F mutation, the most frequent genetic abnormality in MPN patients, in impairing replication fork progression during cell division of MPN patient-derived tumor cells. Moreover, analysis of different MPN disease subtypes reveals unexpected differences in DNA repair activity in response to JAK2V617F-induced perturbations in replication dynamics. These findings have potential implications for tumor clonal evolution and individualized cancer therapy.