β-catenin nuclear translocation in colorectal cancer cells is suppressed by PDE10A inhibition, cGMP elevation, and activation of PKG.

BACKGROUND

The clinical utility of procalcitonin (PCT) and proadrenomedullin (ProADM) in children with malignancies remains inadequately characterized. This study was designed to assess baseline PCT and ProADM levels at the time of leukemia diagnosis and to compare their profiles during subsequent episodes of febrile neutropenia (FN).

METHODS

Children aged 18 years or younger with newly diagnosed acute leukemia, including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), were prospectively recruited for this study. Serum levels of PCT and ProADM were measured at baseline, prior to the initiation of chemotherapy at the time of diagnosis, and were reassessed during subsequent episodes of FN.

RESULTS

A total of 80 children with acute leukemia were prospectively enrolled, with a median age of 5 years (interquartile range [IQR]: 3-7 years). The study population comprised of ALL in 67.5% of cases and AML in 32.5%. At the time of diagnosis, prior to chemotherapy initiation (n=80), the median serum PCT level was 0.19 ng/mL (IQR: 0.07-0.54), while the median ProADM level was 0.04 nmol/L (IQR: 0.01-0.07). Among the 80 patients, 32 children subsequently developed FN and had paired serum samples available for comparative analysis. During FN episodes, both biomarkers showed a significant increase relative to baseline values. Median PCT increased from 0.16 ng/mL (0.08-0.52) at diagnosis to 0.32 ng/mL (0.08-0.50) during FN (P = 0.03), while median ProADM increased from 0.03 nmol/L (0.006-0.05) to 0.41 nmol/L (0.20-0.81) (P < 0.001). At the time of leukemia diagnosis, splenomegaly was the only clinical factor significantly associated with elevated baseline PCT levels (P = 0.010). Subgroup analysis revealed distinct biomarker patterns: in children with ALL, PCT levels remained largely unchanged between diagnosis and FN, possibly reflecting an underlying baseline inflammatory state, whereas ProADM showed a significant rise during FN, suggesting greater specificity for infectious events. In contrast, in AML, both PCT and ProADM increased significantly during FN, indicating their potential utility as infection-related biomarkers in this subgroup.

CONCLUSION

Both PCT and ProADM were significantly elevated in FN when patients with acute leukemia were analyzed as a whole. However, subgroup analysis revealed differing patterns: in ALL, only ProADM remained significantly associated with FN, whereas PCT showed no significant association. In contrast, in AML, both biomarkers were significantly elevated. These findings suggest that ProADM may have greater clinical utility in guiding the management of febrile episodes, particularly in ALL.