Novel oncogene hnRNPK identified for B-cell lymphomas

Researchers at MD Anderson Cancer Center have defined a new oncogene for B-cell lymphomas. The cancer-causing gene, known as heterogeneous ribonucleoprotein K (hnRNPK), appears to lead to cancer development when overexpressed and may lead to new methods for assessing patients and to the development of new lymphoma treatment approaches.

Findings from the study, led by Sean Post, Ph.D., associate professor of Leukemia at MD Anderson, are published online issue of the Journal of the National Cancer Institute.

Using clinical samples, mouse models, global screening assays and biochemical studies, Post and co-first author Prerna Malaney, Ph.D., postdoctoral fellow at MD Anderson, led a team that revealed hnRNPK’s oncogenic potential stems from its ability to regulate a common oncogene called MYC, which is often linked to blood cancers.

“Our findings could have far-reaching implications for lymphoma patients, particularly those who do not harbor MYC amplification or translocations and who may benefit from hnRNPK screening for the purposes of risk stratification and enrollment in potential clinical trials,” says Post.

New mechanism for c-MYC activation

Study results indicated that hnRNPK is a bona fide oncogene when overexpressed and represents a novel mechanism for c-MYC activation in the absence of MYC lesions. According to Post, the finding is significant given that hnRNPK is incorrectly expressed in cancers, and is overexpressed in patients with diffuse large B-cell lymphoma who do not present with MYC genomic alterations.

“Such overexpression is often associated with poor overall survival and progression-free survival,” says Miguel Gallardo, Ph.D., co-first author of the JNCI paper, and former postdoctoral fellow at MD Anderson, who is now at the Centro Nacional de Investigaciones Oncológicas in Madrid. “This was backed up by findings that showed overexpression of hnRNPK in transgenic mice resulted in development of lymphomas and reduced survival.”

The hnRNPK oncogene is known to regulate a multitude of cellular processes and has been implicated in disease development with either increased or reduced expression. Elevated expression of hnRNPK also has been observed in patients with high-grade solid tumors. These observations alluded to an oncogenic function of hnRNPK, but whether elevated hnRNPK levels can independently act as a driver of cancer was unknown, until this study.

The study was funded by the National Institutes of Health (CA016672, R01CA138688, and 1RC1CA146299); the Cancer Prevention and Research Institute of Texas; the Leukemia & Lymphoma Society; the Jane Coffin Childs Memorial Fund for Medical Research; and Cancer Research Innovation Spain. There are no disclosures reported.