ALK- anaplastic large cell lymphoma showed a strong correlation between PD-L1 expression and STAT3 activation (measured by pSTAT3<sup>Tyr705</sup>) (r = 0.8, p < 0.0001).
Using nucleophosmin-anaplastic lymphoma kinase-positive (NPM-ALK<sup>+</sup>) anaplastic large-cell lymphoma (ALCL) as model system, we found in cells and patient-derived tumor xenografts that STAT3 is constitutively acetylated as a result of ALK activity.
Cytokines, their receptors, and downstream signaling partners, especially JAK1/2 and STAT3, are key biomarkers in lymphoproliferative disorders including systemic anaplastic large cell lymphoma (ALCL).
Overall, these results show that IRF4 is involved in STAT3-oncogenic signaling and its inhibition provides alternative avenues for the design of novel/combination therapies of ALCL.
Pyrimidine tract-binding protein 1 mediates pyruvate kinase M2-dependent phosphorylation of signal transducer and activator of transcription 3 and oncogenesis in anaplastic large cell lymphoma.
We speculate that the microRNA-17~92 cluster is involved in lymphomagenesis of STAT3(+) ALCL and that its inhibition might represent an alternative avenue to interfere with ALK signaling in anaplastic large cell lymphomas.
These unique features, which are strictly dependent on NPM-ALK activity and expression, include perpetual cell growth, proliferation, and survival; activation of the key signal transduction pathways STAT3 and mTORC1; and expression of CD30 (the hallmark of anaplastic large-cell lymphoma) and of immunosuppressive cytokine IL-10 and cell-surface protein PD-L1/CD274.
One of the characteristic features of anaplastic lymphoma kinase (ALK)(+), anaplastic large cell lymphoma (ALK(+)ALCL) is the constitutive activation of signal transducers and activators of transcription-3 (STAT3), a defect believed to be important for the pathogenesis of these tumors.
The high frequency of Mcl-1, Bcl-2, and Bcl-X(L) positive ALCL cases in the ALK- group compared with the ALK+ group indicates that ALK induced STAT3 activation is not the main regulatory pathway in ALCL.
Given that survivin is a target of the STAT3 signaling pathway and STAT3 is activated in ALCL, survivin expression was also correlated with STAT3 activation.
We further evaluated the relationship between TIMP1 expression and STAT3 activation in 43 ALCL tumors (19 ALK(+) and 24 ALK(-)) using immunohistochemistry and a tissue microarray.
We further evaluated the relationship between TIMP1 expression and STAT3 activation in 43 ALCL tumors (19 ALK(+) and 24 ALK(-)) using immunohistochemistry and a tissue microarray.