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Hyperactivated STAT3 in ALK-positive diffuse large B-cell lymphoma with clathrin-ALK fusion
Shuji Momose1, Jun-ichi Tamaru, Hirohisa Kishi
1Department of Pathology, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama 350-8550, Japan. momose@saitama-med.ac.jp
Human Pathology
|August 30, 2008
Summary
Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma (DLBCL) with clathrin-ALK fusion shows activated STAT3 signaling. This rare cancer subtype exhibits distinct STAT protein profiles compared to ALK-negative DLBCL.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma (DLBCL) is a rare hematologic malignancy.
- Most cases involve a t(2;17)(p23;q23) translocation, creating a clathrin-ALK fusion gene.
Observation:
- Two cases of ALK-positive DLBCL with clathrin-ALK fusion were analyzed.
- Morphologic and immunohistochemical features included positivity for ALK, IgA, CD138, MUM1, and weak CD30/CD79a, with negativity for CD20.
- The clathrin-ALK transcript was confirmed via RT-PCR and sequencing.
Findings:
- Highly hyperphosphorylated STAT3 (on tyrosine 705) was detected, while STAT5 remained unphosphorylated.
- STAT5A expression was absent in ALK-positive cases but present in some ALK-negative DLBCLs.
- No significant association was found between ALK positivity and the expression of antiapoptotic proteins survivin or BCL-X(L).
Implications:
- STAT3 activation appears crucial in lymphomagenesis for DLBCL with clathrin-ALK fusion.
- Similar STAT protein signaling mechanisms may underlie DLBCL subtypes with different ALK fusion genes.
- Understanding these pathways could inform targeted therapies for rare DLBCL variants.
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