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Haematologica. 2011 Mar;96(3):464-7. doi: 10.3324/haematol.2010.033514. Epub 2010 Dec 6.

Identification of a novel fusion, SQSTM1-ALK, in ALK-positive large B-cell lymphoma.

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Pathology Project for Molecular Targets, Cancer Institute, Japanese Foundation for Cancer Research. 3-8-31 Ariake, Koto, Tokyo 135-8550, Japan.


ALK-positive large B-cell lymphoma is a rare subtype of lymphoma, and most cases follow an aggressive clinical course with a poor prognosis. We examined an ALK-positive large B-cell lymphoma case showing an anti-ALK immunohistochemistry pattern distinct from those of 2 known ALK fusions, CLTC-ALK and NPM-ALK, for the presence of a novel ALK fusion; this led to the identification of SQSTM1-ALK. SQSTM1 is an ubiquitin binding protein that is associated with oxidative stress, cell signaling, and autophagy. We showed transforming activities of SQSTM1-ALK with a focus formation assay and an in vivo tumorigenicity assay using 3T3 fibroblasts infected with a recombinant retrovirus encoding SQSTM1-ALK. ALK-inhibitor therapies are promising for treating ALK-positive large B-cell lymphoma, especially for refractory cases. SQSTM1-ALK may be a rare fusion, but our data provide novel biological insights and serve as a key for the accurate diagnosis of this rare lymphoma.

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