Characterization of the impact of the MYBBP1A gene and rs3809849 on asparaginase sensitivity and cellular functions.

ABSTRACT

Aims: To investigate the role of MYBBP1A gene and rs3809849 in pancreatic cancer (PANC1) and lymphoblastic leukemia (NALM6) cell lines and their response to asparaginase treatment. Materials & methods: The authors applied CRISPR-Cas9 to produce MYBBP1A knock-out (KO) and rs3809849 knock-in (KI) cell lines. The authors also interrogated rs3809849's impact on PANC1 cells through allele-specific overexpression. Results: PANC1 MYBBP1A KO cells exhibited lower proliferation capacity (p ≤ 0.05), higher asparaginase sensitivity (p = 0.01), reduced colony-forming potential (p = 0.001), cell cycle blockage in S phase, induction of apoptosis and remarkable morphology changes suggestive of an epithelial-mesenchymal transition. Overexpression of the wild-type (but not the mutant) allele of MYBBP1A-rs3809849 in PANC1 cells increased asparaginase sensitivity. NALM6 MYBBP1A KO displayed resistance to asparaginase (p < 0.0001), whereas no effect for rs3809849 KI was noted. Conclusions:MYBBP1A is important for regulating various cellular functions, and it plays, along with its rs3809849 polymorphism, a tissue-specific role in asparaginase treatment response.