Lymphoplasmacytoid lymphoma

strong surface expression of the CD30 (Ki-1) antigen, a cytokine receptor in the tumor necrosis factor receptor family. The majority of ALCL demonstrate T-cell surface markers and/or clonal rearrangements of the T-cell receptor locus. There are two main clinical forms: systemic and cutaneous. The cutaneous form is particularly indolent. While it is clinically aggressive, systemic ALCL is generally sensitive to chemotherapy. Approximately 30% of those diagnosed die of the disease.

Approximately 50% of the systemic ALCL carry the t(2;5), which confers a good prognosis. Long-term survival of t(2;5)-positive patients is 80% while that of t(2;5)-negative patients is 25%. The t(2;5)(p23;q35) results in a chimeric gene encoding a fusion of the nucleophosmin (NPM) and anaplastic lymphoma kinase (ALK) proteins. NPM is a multifunctional protein which has been implicated in ribosome assembly, control of centrosome duplication, and nuclear transport as a shuttle protein; it also possesses chaperonin and ribo-nuclease activities. ALK is a member of the insulin family of receptor tyrosine kinases. Its natural ligand is unknown. The NPM-ALK fusion contains the oligomerization domain of NPM and the tyrosine kinase domain of ALK. It results in a self-oligomerizing, constitutively active tyrosine kinase with transforming properties. NPM-ALK can activate numerous downstream effectors, including phospholipase C-y phopho-inositol 3'-kinase and RAS.

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