We assessed ALK genomic status in tumour tissue and used quantitative RT-PCR to measure NPM-ALK fusion transcript in bone marrow and blood samples of patients with anaplastic large-cell lymphoma.
In children, systemic anaplastic large cell lymphomas often present at advanced clinical stage and harbor translocations involving the anaplastic lymphoma kinase (ALK) gene leading to the expression of chimeric anaplastic lymphoma kinase (ALK)-fusion proteins.
This prognostic effect was strongly related to anaplastic lymphoma kinase (ALK) status: ALK-positive ALCL had significantly higher levels of active caspase 3, while high expression of the antiapoptotic proteins Bcl-2 and PI9 was almost completely restricted to ALK-negative cases.
In conclusion, we identified a new subclass of ALK-negative ALCL characterized by aberrant expression of ERBB4-truncated transcripts carrying intronic 5' untranslated regions.
Crizotinib induces apoptosis and gene expression changes in ALK+ anaplastic large cell lymphoma cell lines; brentuximab synergizes and doxorubicin antagonizes.
A distinct pathologic entity characterized by expression of the anaplastic lymphoma kinase (ALK) protein (hence described as ALK lymphoma) has emerged within the heterogeneous group of CD30 anaplastic large-cell lymphomas.
The molecular signature of ALK- ALCL included overexpression of CCR7, CNTFR, IL22, and IL21 genes but did not provide any obvious clues to the molecular mechanism underlying this tumor subtype.
Primary nodal biopsies of 42 patients with ALCL were investigated for the percentage of activated CTLs (quantified using Q-PRODIT) and the expression of ALK by immunohistochemistry using monoclonal antibodies (MoAbs) directed against T-cell antigen granzyme B (GrB) and ALK, respectively.
Conversely, inhibition of ALK activity in NPM-ALK(+) ALCL cells resulted in a concentration-dependent dephosphorylation of JNK and cJun and decreased AP-1 DNA-binding.
Although all ALCL examined were found positive for hTERT expression with RT-PCR, hTERT mRNAs were identified in 68% of these tumors with ISH, with a higher incidence in the group bearing ALK translocations (10 out of 11; 90.9%) compared to the ALK negative group (17 out of 27; 59.3%) (PPearson's = 0.002).
Anaplastic large cell lymphoma (ALCL) exhibiting the t(2;5) translocation is characterized by the resulting expression of the oncogenic fusion protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) gene product.
Anaplastic lymphoma kinase (ALK) constitutes a part of the oncogenic fusion proteins nucleophosmin-ALK and echinoderm microtubule-associated protein like 4-ALK, which are aberrantly expressed in a subset of T-cell anaplastic large-cell lymphoma and non-small-cell lung cancer, respectively.
We report a case of systemic T-cell anaplastic large cell lymphoma CD30+ ALK- with CNS involvement at the time of diagnosis and unusual MRI characteristics resembling acute disseminated encephalomyelitis.
These cells expressed ALK protein, but, in contrast to t(2;5)-positive ALCL (which show cytoplasmic, nuclear, and nucleolar staining), labeling was restricted to the malignant cell cytoplasm.
These results show how ALCL cases that express ALK proteins other than NPM-ALK can be detected by sensitive biochemical techniques using routine cryostat sections.
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.