PHF19 Promotes Drug Resistance via Increased EZH2 Phosphorylation in Multiple Myeloma

PHD finger protein 1 9(PHF19), represents a potential therapeutic target to overcome drug resistance and improve outcomes of multiple myeloma (MM) patients, according to a study presented at the 17th International Myeloma Workshop.

Researchers assessed the expression of PHF19, a component of the polycomb repressive complex 2, as well as outcomes of MM patients in clinical databases and sequential patient samples. They confirmed the effects of PHF19 on cell growth and drug resistance by overexpression both in vitro and in vivo, respectively. They also used co-IP and western blot assay to confirm molecular mechanism involved in PHF19 functionality.

The study results showed that enhanced PHF19 expression is highly linked to high-risk cytogenetic profiles and inferior outcomes of MM patients. They observed that PHF19OE notably enhanced cell proliferation juxtaposed to cells transfected with an empty vector (EV) in both ARP1 and OCI-My5 MM cell lines. They also found that the overexpression of PHF19 led to suppression of apoptosis in ARP1 and OCI-My5 cells exposed to commonly using anti-MM reagents, such as bortezomib (BTZ), epirubicin (EPI), and melphalan (MEL).

The researchers also used a xenograft mouse model to evaluate the effects of PHF19 overexpression, and observed that mice engrafted ARP1OE cells had a perceptibly larger tumor volume than the control mice engrafted with ARP1-EV cells. They noted that “consistent with our in vitro data, bortezomib injection could not inhibit ARP1-OE cell growth.” Overall, the results showed that PHF19 promotes MM cell growth and drug resistance both in vitro and in vivo.

“Deregulation of miR15a/PHF19/phosphorylation EZH2 patterns participates in disease pathogenesis and progression of MM,” the research authors wrote in their conclusion. “Our data provides preclinical rational to support the treatment targeting PHF19 to suppress growth and overcome drug resistance in MM and other cancers.”

Yu T, et al. PHF19 Promotes Drug Resistance via Increased EZH2 Phosphorylation in Multiple Myeloma. Presented at the 17th International Myeloma Workshop; September 12-15, 2019; Boston, MA.