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 IgVH (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 IgVH 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.