Mutational analysis of IκBα in hematologic malignancies

The activation of the NF-κB family of transcription factors plays a crucial role in oncogenesis. The IκB family has the ability to retain the NF-κB in an inactive complex in the cytoplasm. Recently, mutations of the IκBα gene were found in Hodgkin's lymphoma, which allows NF-κB proteins to translocate into the nucleus in an active form. In this report, we describe a mutational analysis of IκBα for primary tumor cells obtained from patients with a variety of hematologic malignancies (acute myelogenous leukemia, chronic myelogenous leukemia, myelodysplastic syndrome, hairy cell leukemia, adult T-cell leukemia, and mantle cell lymphoma) as well as 15 leukemia, lymphoma, and myeloma cell lines (HL60, U937, HEL, K562, NALM1, Jurkat, JM, MOLT4, Raji, KS1, OKM2T, OKM3T, F6T, Su9T01, and C2-2). RT-PCR, followed by direct sequencing, was performed and all samples expressed IκBα. One missense mutation was identified in a primary effusion lymphoma cell line, KS1. However, NF-κB (p65) protein was absent from the nucleus of KS1 immunohistochemically, suggesting that the mutation did not alter the function of IκBα in this case. Taken together, although it is not clear whether normal IκBα protein was expressed in hematologic malignancies, mutations of IκBα could be rare events in these diseases, except for Hodgkin's lymphoma. Alterations of other members of NF-κB/ IκB family proteins might act on the development of hematologic malignancies.