Neuropeptide Y (NPY) synthesis in lymphoblasts and increased plasma NPY in pediatric B-cell precursor leukemia

Abstract

Neuropeptide Y (NPY), a regulatory peptide in both the central and peripheral nervous systems, has recently been found in neuroendocrine tumors as well as in the bone marrow of rat and certain autoimmune mice, but not in human bone marrow. To investigate a possible role for NPY in the human hematopoietic system, we have prospectively studied NPY-like immunoreactivity in plasma (P-NPY-LI) and NPY mRNA in bone marrow from children with acute leukemia. Northern blot showed high levels of NPY mRNA in bone marrow and peripheral lymphoblasts from children with B-cell precursor leukemia. In situ hybridization showed NPY mRNA in malignant B-cell precursor lymphoblasts. No NPY mRNA was detected in the bone marrow of children with T-cell leukemia. P-NPY-LI was higher (P less than .001) in 51 children with leukemia (200:50 to 385 pmol/L, median:interquartile range) compared to 51 age-matched healthy controls (37:20 to 52 pmol/L). P-NPY-LI was higher (P less than .001) in those with favorable clinical risk classification. Elevated P- NPY-LI, compared with the upper age-adjusted reference limit, was only found in children with B-cell precursor leukemia (31 of 40), whereas all children with B-cell, T-cell, or myeloid leukemia (n = 11) had normal P-NPY-LI (P less than .001). During the 2- to 46-month follow- up, children with elevated P-NPY-LI had better (P less than .001) outcome compared to those with normal P-NPY-LI (79.4% v 34.6% probability for event-free survival).