Dual targeting of transformed and untransformed HTLV-1-infected T cells by DHMEQ, a potent and selective inhibitor of NF-kappaB, as a strategy for chemoprevention and therapy of adult T-cell leukemia.

Human T-cell leukemia virus type I (HTLV-1) causes adult T-cell leukemia (ATL), a fatal T-cell leukemia resistant to chemotherapy, after more than 50 years of clinical latency from transmission through breast-feeding. Polyclonal expansion of virus-infected T cells predisposes them to transformation. Constitutive activation of nuclear factor-kappaB (NF-kappaB) in the leukemic cells is essential for their growth and survival.

The clonal expansion of human T lymphotropic virus type 1-infected T cells: a comparison between seroconverters and long-term carriers.

Background: The clonal expansion of human T lymphotropic virus type 1 (HTLV-1)-infected T cells is considered to be important for the maintenance of infection. However, the process by which the clonality of HTLV-1-infected T cells is established is not understood.

Methods: HTLV-1 clonality in 4 adult seroconverters was analyzed by inverse long polymerase chain reaction (PCR) followed by cloning of the PCR products and evaluation of restriction fragment-length polymorphism.

The NPM-ALK oncoprotein abrogates CD30 signaling and constitutive NF-kappaB activation in anaplastic large cell lymphoma.

NPM-ALK characterizes anaplastic large cell lymphoma (ALCL), as does the high expression of CD30, a feature shared with H-RS cells of classic Hodgkin's lymphoma. In H-RS cells, ligand-independent signaling by overexpressed CD30 drives constitutive NF-kappaB activation, which is absent in ALCL cells. Here we show that NPM-ALK impedes CD30 signaling and NF-kappaB activation, dependent on both ALK kinase activity and the N-terminal NPM domain.