Jak3 activation is significantly associated with ALK expression in anaplastic large cell lymphoma.

Abstract

Janus kinase 3 (Jak3) is a tyrosine kinase that activates signal transducer and activator of transcription 3 (Stat3) in response to cytokine stimulation. Stat3 is an oncogene. In previous studies of anaplastic large cell lymphoma (ALCL), we showed that inhibition of Jak3 down-regulates activated/phosphorylated Stat3 (pStat3), decreases anaplastic lymphoma kinase (ALK) enzymatic activity, and induces cell-cycle arrest and apoptosis in ALK-positive ALCL. These findings implicate Jak3 as playing a significant role in the pathogenesis of ALK-positive ALCL; most likely via Stat3 and ALK activation. To assess this possibility, we used immunohistochemical staining to evaluate the frequency of expression of Jak3 and its activated/phosphorylated form (pJak3) in 48 systemic ALCL tumors included in a tissue microarray. pJak3 was detected in 17 (81%) of 21 ALK-positive tumors, compared with 3 (11%) of 27 ALK-negative tumors (P < .0001, Fisher exact test). pStat3 was present in 12 (86%) of 14 ALK-positive tumors and in 10 (40%) of 25 ALK-negative tumors assessed (P = .0078). Of 12 ALK-positive/pStat3-positive tumors, 8 (67%) expressed pJak3, but none of 10 ALK-negative/pStat3-positive tumors expressed pJak3. We conclude that Jak3 activation is predominantly restricted to ALK-positive ALCL tumors. Most likely, Jak3 collaborates with ALK in activating Stat3, leading to cell survival, cell-cycle progression, and tumor growth. In contrast, the mechanism of Stat3 activation in ALK-negative ALCL tumors appears to be independent of Jak3.

• Authors: Raymond Lai, George Z Rassidakis, Quan Lin, Coralyn Atwell, L Jeffrey Medeiros, Hesham M Amin
• Journal: Human pathology (Hum Pathol) Vol. 36 Issue 9 Pg. 939-44 (Sep 2005) ISSN: 0046-8177 [Print] United States
• PMID: 16153455 (Publication Type: Journal Article)

Chemical References

• ALK protein, human
• Anaplastic Lymphoma Kinase
• Protein-Tyrosine Kinases
• Receptor Protein-Tyrosine Kinases
• JAK3 protein, human
• Janus Kinase 3

Topics

• Adolescent
• Adult
• Anaplastic Lymphoma Kinase
• Child
• Enzyme Activation
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Janus Kinase 3
• Lymphoma, Large B-Cell, Diffuse (enzymology)
• Male
• Middle Aged
• Phosphorylation
• Protein-Tyrosine Kinases (metabolism)
• Receptor Protein-Tyrosine Kinases