Parathyroid Hormone-Related Protein in Adult T-Cell Leukemia-Lymphoma

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Abstract
Objective: To determine whether parathyroid hormone-related protein is synthesized and secreted by the tumor cells of patients with adult T-cell leukemia-lymphoma. Design and Patients: Convenience sample of three patients with adult T-cell leukemia-lymphoma. Two patients developed hypercalcemia, and one patient was normocalcemic. Setting: Inpatient facilities at two university-affiliated medical centers. Intervention: All patients had a lymph node biopsy. In addition, samples of ascitic or pleural fluid, or both, were obtained from these patients. Measurements and Results: Using RNA blot analysis, we showed that parathyroid hormone-related protein (PTHrP) messenger RNAs (mRNAs) were constitutively expressed in the tumor cells from all patients. Cyclic adenosine monophosphate (cAMP) production-stimulating activity, assessed using osteoblast-like UMR106 cells, was demonstrated in the pleural and ascitic fluids from the two patients who developed hypercalcemia. The elution profiles of the cAMP production-stimulating activity in the ascitic fluid extracts were very similar to those of the tumor extracts from hypercalcemic nude rats that had been implanted with a human cancer tumor. Conclusions: Parathyroid hormone-related protein is produced by tumor cells in adult T-cell leukemia-lymphoma, which may be an important factor in the development of hypercalcemia in the patients with this disease. However, the development of hypercalcemia may depend on other factors such as the number of tumor cells, access of the protein into systemic circulation, and the presence of some additional substances.

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