Mutational analysis of IkappaBalpha in hematologic malignancies.
The activation of the NF-kappaB family of transcription factors plays a crucial role in oncogenesis. The IkappaB family has the ability to retain the NF-kappaB in an inactive complex in the cytoplasm. Recently, mutations of the IkappaBalpha gene were found in Hodgkin's lymphoma, which allows NF-kappaB proteins to translocate into the nucleus in an active form. In this report, we describe a mutational analysis of IkappaBalpha 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 IkappaBalpha. One missense mutation was identified in a primary effusion lymphoma cell line, KS1. However, NF-kappaB (p65) protein was absent from the nucleus of KS1 immunohistochemically, suggesting that the mutation did not alter the function of IkappaBalpha in this case. Taken together, although it is not clear whether normal IkappaBalpha protein was expressed in hematologic malignancies, mutations of IkappaBalpha could be rare events in these diseases, except for Hodgkin's lymphoma. Alterations of other members of NF-kappaB/ IkappaB family proteins might act on the development of hematologic malignancies.
Hatta
Yoshihiro
Y
Department of Internal Medicine, Division 1, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan. yhatta@med.nihon-u.ac.jp
Arima
Naomichi
N
Machino
Tatsuya
T
Itoh
Takeysohi
T
Hashimoto
Shu
S
Takeuchi
Jin
J
Sawada
Umihiko
U
Hayakawa
Satoshi
S
Yamamoto
Tatsuo
T
Horie
Takashi
T
D004252:DNA Mutational Analysis; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D000072000:NF-KappaB Inhibitor alpha
D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha