Abstract
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.
MeSH terms
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3T3 Cells
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Adaptor Proteins, Signal Transducing / genetics*
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Adaptor Proteins, Signal Transducing / metabolism
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Amino Acid Sequence
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Anaplastic Lymphoma Kinase
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Animals
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Cell Transformation, Viral
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Cyclophosphamide / administration & dosage
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Cyclophosphamide / therapeutic use
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Doxorubicin / administration & dosage
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Doxorubicin / therapeutic use
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Humans
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Immunohistochemistry
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In Situ Hybridization, Fluorescence
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Injections, Subcutaneous
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Lymphoma, Large B-Cell, Diffuse / diagnosis
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Lymphoma, Large B-Cell, Diffuse / drug therapy
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Lymphoma, Large B-Cell, Diffuse / genetics*
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Lymphoma, Large B-Cell, Diffuse / pathology
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Male
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Mice
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Mice, Nude
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Middle Aged
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Molecular Sequence Data
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Oncogene Proteins, Fusion / genetics*
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Oncogene Proteins, Fusion / metabolism
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Polymerase Chain Reaction
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Prednisolone / administration & dosage
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Prednisolone / therapeutic use
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Receptor Protein-Tyrosine Kinases / genetics*
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Receptor Protein-Tyrosine Kinases / metabolism
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Retroviridae
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Sequestosome-1 Protein
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Signal Transduction / genetics
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Vincristine / administration & dosage
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Vincristine / therapeutic use
Substances
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Adaptor Proteins, Signal Transducing
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Oncogene Proteins, Fusion
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SQSTM1 protein, human
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Sequestosome-1 Protein
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Vincristine
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Doxorubicin
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Cyclophosphamide
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Prednisolone
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ALK protein, human
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Alk protein, mouse
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Anaplastic Lymphoma Kinase
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Receptor Protein-Tyrosine Kinases