Protein Kinase D 1 Predicts Poor Treatment Response and Unfavorable Survival of Bortezomib-Based Treatment, and Its Knockdown Enhances Drug Sensitivity to Bortezomib in Multiple Myeloma

Abstract

Objective: The present study aimed to explore the correlation of protein kinase D 1 with prognosis in bortezomib-treated multiple myeloma patients and further investigate the effect of protein kinase D 1 knockdown on drug sensitivity to bortezomib in multiple myeloma cells. Methods: Totally, 104 de novo symptomatic multiple myeloma patients treated with bortezomib-based regimens and 30 healthy controls were recruited. Bone marrow mononuclear cells–derived plasma cells were collected from multiple myeloma patients before initial treatment and from healthy controls on the bone marrow donation, respectively, then protein kinase D 1 protein/messenger RNA expressions were detected by Western blot and reverse transcription quantitative polymerase chain reaction, respectively. The effect of protein kinase D 1 knockdown on drug sensitivity to bortezomib was detected by transfecting protein kinase D 1 knockdown plasmid and control plasmid into RPMI8226 and U266 cells. Results: Protein kinase D 1 protein/messenger RNA expressions were both upregulated in multiple myeloma patients compared with healthy controls and presented good value in differentiating multiple myeloma patients from healthy controls. Furthermore, protein kinase D 1 protein/messenger RNA expressions were both associated with high International Staging System stage and t (4; 14). Furthermore, both complete response rate and overall response rate were reduced in protein kinase D 1 high patients compared with protein kinase D 1 low patients; similarly, progression-free survival and overall survival were both decreased in protein kinase D 1 high patients compared with protein kinase D 1 low patients. In addition, in RPMI8226 and U266 multiple myeloma cells, protein kinase D 1 knockdown increased drug sensitivity to bortezomib. Conclusion: Protein kinase D 1 has the potential to predict poor treatment response and unfavorable survival of bortezomib-based treatment in multiple myeloma patients, and its knockdown enhanced drug sensitivity to bortezomib in multiple myeloma cells.