Ny artikkel fra Håkon Reikvam

Håkon Reikvam

Crit Rev Oncog. 2009;15(1):1-36.

Nuclear Factor-kappaB Signaling: A Contributor in Leukemogenesis and a Target for Pharmacological Intervention in Human Acute Myelogenous Leukemia.
Reikvam H, Olsnes AM, Gjertsen BT, Ersvar E, Bruserud O.

Division for Hematology, Institute of Medicine, University of Bergen, Bergen, Norway.

Acute myeloid leukemia (AML) is an aggressive malignancy with only 40 - 50% long-term survival even for younger patients who can receive the most aggressive therapy. For elderly patients who only receive palliative treatment, the median survival is only 2-3 months. Inhibition of the nuclear factor-kappaB (NF-kappaB) transcription factor family is one of the therapeutic strategies that are considered in AML. NF-kappaB is an important regulator of several biological processes that are involved in leukemogenesis, including proliferation differentiation, autophagy, and apoptosis. Constitutive NF-kappaB activation has been detected in AML cells and NF-kappaB inhibition is therefore a possible therapeutic strategy in AML. Multiple pharmacological agents have shown inhibitory effects against NF-kappaB signaling pathways, including proteasome inhibitors as well as the more-specifc agents that are directed against various steps of this signaling pathway. Recent studies strongly suggest that primary human AML cells (including AML stem cells) are susceptible to NF-kappaB inhibition, but this therapeutic approach should possibly be combined with other therapeutic agents to achieve a combined effect both on NF-kappaB transcriptional activity, tumor suppressor-induced signaling, and stress-induced pathways. The clinical documentation with regard to the effciency and safety of NF-kappaB inhibition is still limited, but experimental evidence strongly suggests that NF-kappaB inhibition should be further investigated in human AML.

Foto: Magnus Blø