05 June 2019

Spanish researchers have identified a promising new target for the treatment of B-cell lymphomas.

Researchers led by Dr Miguel Gallardo at the Spanish National Cancer Research Centre, Madrid, Spain, examined samples from patients with diffuse large B-cell lymphoma. They found that high levels of a protein called hnRNP K were associated with “dismal” long-term survival.

They subsequently discovered in mice that overproducing hnRNP K selectively in B cells can trigger the development of lymphoma.

Previous work had shown that this protein regulates many cellular processes, and both its over- and under-production are involved in the development of various cancers. This new work confirms the tumour-promoting function of hnRNP K for B-cell lymphomas, the researchers say.

The researchers identified that high levels of hnRNP K in B cells led to the overproduction of c-Myc, a known driver of B-cell lymphoma. However, hnRNP K-positive cells were also sensitive to inhibitors which block the BET-bromodomain, which points to a novel avenue for treatment of some B-cell lymphomas.

Dr Gallardo said: “Overexpression of hnRNP K is often associated with poor recovery and low survival rates. This was confirmed by findings that overexpression of hnRNP K in transgenic mice resulted in development of lymphoma and reduced survival.”

The study was published in the Journal of the National Cancer Institute.

The authors write: “We and others have previously shown that reduced hnRNP K expression down-modulates tumour suppressive programs. However, over-expression of hnRNP K is the more commonly observed clinical phenomenon, yet its functional consequences and clinical significance remain unknown.

“Our findings indicate that hnRNP K is a bona fide oncogene when overexpressed and represents a novel mechanism for c-Myc activation in the absence of MYC lesions.”

The team believe this discovery may lead to new methods for assessing patients and to the development of novel treatments.

Source: Gallardo, M, Malaney, P, Aitken, M.J.L., Zhang, X., Link, T.M., Shah, V., Alybayev, S., Wu, M.H., Pageon, L.R., Ma, H., Jacamo, R., Yu, L., Xu-Monette, Z.Y., Steinman, H., Lee, H.J., Sarbassov, D., Rapado, I., Barton, M.C., Martinez-Lopez, J., Bueso-Ramos, C., Young, K.H., Post, S.M. (2019) “Uncovering the role of hnRNP K, an RNA-binding protein, in B-cell lymphomas”, Journal of the National Cancer Institute, available from doi: 10.1093/jnci/djz078


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