Our findings highlight the STAT5 dependent transcriptional regulation of Dpf3, demonstrating for the first time increased STAT5 activation in non-malignant myeloid cells of CLL patients and open novel routes of investigation to facilitate the understanding of the role of activated STAT5 in non-malignant myeloid and malignant B-cells communication. Here, DPF3 is linked to B-cell chronic lymphocytic leukemia.