Cell cycle genes co-expression in multiple myeloma and plasma cell leukemia

- Co-expression of activator and inhibitor gene sets is in dynamic equilibrium.
- Inhibitor gene set is more sensitive to the activators changes, not vice versa.
- CDKN2A overexpression is associated with shorter OS in newly diagnosed MM patients.
- CDKN2A overexpression is associated with shorter TTP in MM patients.

The objective of this study was to describe co-expression correlations of cell cycle regulatory genes in multiple myeloma (MM) and plasma cell leukemia (PCL).Our results highlight the presence of dynamic equilibrium between co-expression of activator and inhibitor gene sets. Moreover inhibitor set is more sensitive to the activator changes, not vice versa. We have shown that CDKN2A expression is associated with short-term survival in newly diagnosed MM patients (survival was 30.3 ± 3.9 months for 'low' expressed and 7.5 ± 5.6 months for 'high' expressed group, p < 0.0001). Moreover low-expression CDKN2A group showed time-to-progression benefit in newly diagnosed patients (remission was 20.8 ± 3.6 months for 'low' and 8.4 ± 2.7 months for 'high' expressed group, p < 0.0001) as well as in whole studied cohort of MM patients (remission was 20.8 ± 2.8 months for 'low' and 9.8 ± 1.1 months for 'high' expressed group, p < 0.0001). The overexpression of inhibitors can be explained as a compensatory reaction to growing “oncogenic stress”.