Serum thrombopoietin compared with ZAP-70 and immunoglobulin heavy-chain gene mutation status as a predictor of time to first treatment in early chronic lymphocytic leukemia

Abstract

In an effort to confirm previous reports we analyzed clinico-biological implications of increased serum levels of thrombopoietin (TPO) in a series of 71 previously untreated Binet stage A B-cell chronic lymphocytic leukemia (CLL) patients. Serum levels of TPO did not correlate with peripheral blood lymphocytosis (p = 0.928), Rai substages (p = 0.516), platelet count (p = 0.572), hemoglobin level (p = 0.228), LDH (p = 0.144) and β₂-microglobulin (p = 0.520). The same applied when correlation with ZAP-70 (p = 0.562), CD38 (p = 0.258) or mutational status of IgV_H (p = 0.0794) were sought. The risk of disease-progression according to known and putative prognostic parameters was also evaluated as time to first treatment (TFT). The univariate Cox proportional hazard model demonstrated that the absence of IgV_H mutational status (p = 0.0005) and ZAP-70-positivity (p = 0.02) were associated with a shorter TFT. In contrast, Kaplan-Meier estimates of TFT, plotted after setting as cut-off the median value for TPO (i.e., 46 pg/mL), failed to demonstrate any statistical difference between two groups (p = 0.342). Looking for cellular source of TPO we investigated the presence of TPO at gene expression level in 60 B-CLL patients belonging to an independent series. Here we provide evidence for the presence of a low TPO gene expression transcript in B-CLL cells. In conclusion, our results indicate that in early B-cell CLL circulating level of TPO does not provide a useful insight into the complex interrelationship of prognostic variables.

Keywords:

• TPO
• early CLL
• ZAP-70
• IgV_H mutational status
• prognosis