For validation, we directed expression of NPM-ALK, the fusion oncogene driving a subset of anaplastic large cell lymphoma (ALCL), to T-cells by infecting hematopoietic stem cells from Lck-Cre-transgenic mice with a retroviral construct containing the NPM-ALK cDNA preceded by a translational stop cassette.
Breast implant-associated ALCL presents as a seroma with a median of 8-10 years after implant placement, lacks the ALK gene translocation and has an overall favourable but variable prognosis, depending on extent of disease at diagnosis and treatment.
Instead, phosphoproteomics and confirmatory functional studies revealed that the STAT1 overactivation is the key mechanism of ALK-TKI addiction in ALCL.
Overall survival was not different between patients with PD-L1+ vs PD-L1- anaplastic large cell lymphoma (p = 0.44), regardless of ALK status and International Prognostic Index (IPI) score.
In this study, we investigated the therapeutic combination of a CD30-targeting ADC (anti-CD30-lidamycin [LDM]) with a small-molecule inhibitor (crizotinib) of nucleophosmin-anaplastic lymphoma kinase NPM-ALK in CD30<sup>+</sup>/ALK<sup>+</sup> anaplastic large cell lymphoma (ALCL).
Herein, we describe a well-characterized case of ALK-negative ALCL with no rearrangement but amplification of DUSP22/IRF4, diagnosed by cytologic examination of the pleural effusion in a 68-year-old white man with a 3-year history of unexplained eosinophilia and pulmonary infiltrates.
Taken together, the novel ALK inhibitor ZYY has tremendous potential for treating human ALCL, and a combination of autophagy and ALK inhibition could effectively elicit potent antitumor effects.
Immunohistochemistry was positive for CD30/CD4 and negative foranaplastic lymphoma kinase, confirming the presence of ALCL, then associated with gluteal implant, an event not described in literature.
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.
ALK is a receptor tyrosine kinase, associated with many tumor types as diverse as anaplastic large cell lymphomas, inflammatory myofibroblastic tumors, breast and renal cell carcinomas, non-small cell lung cancer, neuroblastomas, and more.
Together, our findings suggest that CDK6 could be a therapeutic target for the development of future treatments for NPM-ALK<sup>+</sup> anaplastic large-cell lymphoma.
Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphomas are tumors that carry translocations involving the <i>ALK</i> gene at the 2p23 locus, leading to the expression of ALK tyrosine kinase fusion oncoproteins.
As a receptor tyrosine kinase of insulin receptor (IR) subfamily, anaplastic lymphoma kinase (ALK) has been validated to play important roles in various cancers, especially anaplastic large cell lymphoma (ALCL), nonsmall cell lung cancer (NSCLC), and neuroblastomas.
Methotrexate significantly induced apoptosis in ALK inhibitor-resistant cells expressing the NPM-ALK mutant harboring the point mutation, G262R, and in ALCL patient-derived NPM-ALK-positive Ki-JK cells.
TYK2 is a member of the JAK family of tyrosine kinases that is involved in chromosomal translocation-induced fusion proteins found in anaplastic large cell lymphomas (ALCL) that lack rearrangements activating the anaplastic lymphoma kinase (ALK).
Anaplastic large cell lymphoma (ALCL) is a type of T-cell lymphoma that can be divided into two categories: anaplastic lymphoma kinase-positive (ALK+) and ALK-negative.Gastrointestinal ALK+ ALCL is rare.
CD30+ lymphoproliferative disorders (LD) represent a spectrum of entities ranging from self-limited proliferations or cutaneous lesions with favorable prognosis, such as lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma (ALCL), to more aggressive malignancies such as systemic ALK-positive and ALK-negative ALCL.
To determine how cancers acquire resistance to ALK inhibitors, we established a model of acquired crizotinib resistance by exposing a highly sensitive NPM-ALK-positive ALCL cell line to increasing doses of crizotinib until resistance emerged.
Additional sequencing for a total of 238 T-NHLs confirmed the specificity of <i>MSC</i><sup>E116K</sup> for ALK<sup>-</sup> ALCL and further demonstrated that 14 of 15 mutated cases (93%) had coexisting <i>DUSP22</i> rearrangements.
Genomic characterization performed in BIA-ALCL to date has demonstrated qualitatively similar molecular abnormalities to those seen in its more common counterpart [ALK-negative systemic anaplastic large cell lymphoma (sALCL)] including JAK/STAT activation and MYC/TP53 dysregulation.