Dr. Apollina Goel
Participation year
Project title

Role of Manganese Superoxide Dismutase in Myeloma Cell Proliferation


Multiple myeloma (MM) is a systemic, plasma cell neoplasm that currently remains incurable. MM tumors frequently exhibit a deregulated expression of D-type cyclins that is rendered by genetic rearrangements. D-type cyclins are known to favor cell proliferation by inducing expression of E-cyclins, which facilitate the passage of cells through the cell cycle restriction point “R” at the G1-S phase boundary. Clinical studies, however, show that MM patients with cyclin D1 overexpression exhibit lower proliferation index suggesting a role of cyclin E, its associated cyclin dependent kinase (cdk)2 or other molecular regulator(s) that may contribute to the uncontrolled proliferation, pathogenesis and/or therapy resistance in MM. Accumulating data have established that myeloma cell survival and disease progression are sustained by pro-inflammatory cytokines secreted in a constitutive fashion, by both paracrine and autocrine mechanisms in the bone marrow microenvironment. Several of the myeloma cell pro-proliferative cytokines such as TNF-a, IL-1_, and IL-6 have been shown to induce superoxide production and also trigger downstream signaling events. Among the various enzymatic antioxidant-defense systems, the mitochondria-localized manganese superoxide dismutase (MnSOD), which converts superoxide to hydrogen peroxide, plays a major role in maintaining cellular antioxidant capacity. A role for MnSOD in MM progression is consistent with the facts that: mice lacking a copy of the SOD2 gene show an increased incidence of spontaneous B cell lymphomas; and both primary human myeloma cells and cells from established myeloma lines express MnSOD protein at low levels. Since cell cycle check-points are controlled by cyclin/cdk complexes, and also by dynamic changes in the reduction and oxidation (redox) status of the cells, this study was designed to evaluate the role on MnSOD overexpression and/or cyclin E knockdown on cell cycle progression in MM cells.

Angela  Torres
UPR @ Aguadilla