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A protein implicated in Crohn’s Disease predisposes the development of a type of lymphoma

International research directed by CIMA suggests that inhibition of NKX2-3 may be a selective therapeutic strategy in marginal-zone lymphomagenesis

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Doctors José A. Martínez Climent and Eloy Robles, researchers at CIMA of the University of Navarra. FOTO: Manuel Castells
29/06/16 09:55 María Pilar Huarte

Scientists at the Center for Applied Medical Research (CIMA) of the University of Navarra have identified a protein which predisposes the development of a type of hematological tumour, marginal-zone lymphomagenesis. The results have been published in the scientific journal Nature Communications.

Marginal-zone lymphomas represent 10% of the B lymphomas, a type of hematological tumour. Currently there are no precise diagnostic markers for this disease. Although in every case a constitutive activation of the B-cells receptor (BCR) has been seen, the mechanism which activates it is unknown in a high percentage.

The research led by CIMA has identified a group of patients with marginal-zone lymphoma who exhibit an anomalous expression of NKX2-3, a protein implicated in the development of Crohn’s Disease, which, up to now, had not been associated with the development of cancer. “This aberrant expression is not detected in other types of lymphomas, so this protein could be a marker for the diagnosis of the disease”, explained the doctors Eloy F. Robles and José A. Martínez Climent, lead author and director of the research, respectively. Researchers from the Centro Nacional de Biotecnología del CSIC (CNB-CSIC) in Madrid and from other centres in the United Kingdom, Hungary, Belgium and Germany are collaborating in this research.

In their work they have described a new transgenic mouse model which develops marginal-zone lymphoma with characteristics that can be superimposed on tumours in patients. “Our results suggest that the NKX2-3 protein activates the BCR in marginal-zone lymphomas, by selective phosphorylation of the SYK and LYN kinases”.

Possible therapeutic strategy

The researchers at CIMA are working on the generation and characterization of genetically modified mice for the development of leukemia, lymphoma B or multiple myeloma similar to the human pathology. Their objective is to study the mechanisms for tumor transformation and to evaluate new in vivo therapies. “We have described experimental models which permit the study of the role of different molecules in other types of hematological tumors, such as mantle cell lymphoma, extranodal marginal lymphoma or diffuse large-cell lymphoma. We hope that this new model will be useful to discover how the BCR signaling is activated in marginal lymphoma. Our work suggests that the selective inhibition of NKX2-3 could deactivate the BCR signaling and, therefore, be used as therapy in this type of lymphoma”, stated the author the work.

Nat Commun. 2016 Jun 14;7:11889. doi: 10.1038/ncomms11889.

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