ChoK-Full of Potential: Choline Kinase in B Cell and T Cell Malignancies

Aberrant choline metabolism, characterized by an increase in total choline-containing compounds, phosphocholine and phosphatidylcholine (PC), is a metabolic hallmark of carcinogenesis and tumor progression. This aberration arises from alterations in metabolic enzymes that control PC biosynthesis and catabolism. Among these enzymes, choline kinase alpha (CHK alpha) exhibits the most frequent alterations and is commonly overexpressed in human cancers. CHK alpha catalyzes the phosphorylation of choline to generate phosphocholine, the first step in de novo PC biosynthesis. CHK alpha overexpression is associated with the malignant phenotype, metastatic capability and drug resistance in human cancers, and thus has been recognized as a robust biomarker and therapeutic target of cancer. Of clinical importance, increased choline metabolism and CHK alpha activity can be detected by non-invasive magnetic resonance spectroscopy (MRS) or positron emission tomography/computed tomography (PET/CT) imaging with radiolabeled choline analogs for diagnosis and treatment monitoring of cancer patients. Both choline-based MRS and PET/CT imaging have also been clinically applied for lymphoid malignancies, including non-Hodgkin lymphoma, multiple myeloma and central nervous system lymphoma. However, information on how choline kinase is dysregulated in lymphoid malignancies is very limited and has just begun to be unraveled. In this review, we provide an overview of the current understanding of choline kinase in B cell and T cell malignancies with the goal of promoting future investigation in this area.

Automated summary

Aberrant choline metabolism, particularly involving overexpression of choline kinase alpha (CHKα), is a metabolic hallmark of carcinogenesis and tumor progression. Non-invasive imaging techniques such as MRS and PET/CT, utilizing radiolabeled choline analogs, can detect increased choline metabolism and CHKα activity, providing valuable diagnostic and monitoring tools for cancer patients.