MDMX/MDM4 is highly expressed and contributes to cell growth and survival in anaplastic large cell lymphoma

Sinatkas, Vaios; Σταθοπούλου, Κωνσταντίνα; Xagoraris, Ioanna; Ye, Jingjing; Vyrla, Dimitra; Atsaves, Vassilios; Leventaki, Vasiliki; Medeiros, L. Jeffrey; Rassidakis, George Z.; Δράκος, Ηλίας

doi:10.1080/10428194.2021.1876871

Cited by 3 publications

(2 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The MDM2/MDM4 dimer polyubiquitinates p53, targeting it for proteasomal degradation, and inhibits p53 transcriptional activity (17). MDM4 amplification and overexpression is seen in hematologic malignancies including acute myeloid leukemia, anaplastic large cell lymphoma and Burkitt lymphoma (21,22). MDM4 knockdown leads to p53 activation and tumor regressions (17), prompting ongoing studies of MDM4 inhibitors (17,23).…”

Section: Discussionmentioning

confidence: 99%

Brentuximab vedotin as a bridge to combination chemotherapy in gray zone lymphoma with severe liver impairment: a case report

Asrani,

Cengiz,

Petersen

et al. 2024

Front. Oncol.

View full text Add to dashboard Cite

BackgroundGray zone lymphoma (GZL) is a rare lymphoma subtype characterized by features intermediate between diffuse large B-cell lymphoma (DLBCL) and classic Hodgkin lymphoma (cHL). The optimal first-line treatment for GZL remains undefined, particularly for patients with poor performance status or baseline organ impairment. Brentuximab vedotin (BV), a targeted therapy that binds to CD30, a TNFR superfamily member involved in NF-kB signaling, has shown promise in the treatment of CD30-positive lymphomas. However, its use in GZL, especially in patients with severe liver impairment, has not been reported previously.Case descriptionWe present a case of a 37-year-old male with GZL and severe liver impairment at initial presentation. The patient initially received monotherapy with BV, which resulted in a marked improvement in liver enzymes and bilirubin levels. Subsequently, combination cytotoxic chemotherapy consisting of dose-adjusted etoposide, prednisone, cyclophosphamide, and doxorubicin (DA-EP_CH) was added. Repeat imaging revealed near complete resolution of lymphadenopathy and significant reduction in hepatosplenomegaly. The patient completed a full course of chemotherapy and achieved a complete response. Follow-up examinations showed no evidence of recurrent disease, and the patient resumed full-time work.DiscussionGZL poses diagnostic challenges due to its overlapping features with DLBCL and cHL. Accurate diagnosis relies on comprehensive histopathological evaluation, immunophenotyping, and molecular analysis. The optimal first-line treatment for GZL remains uncertain. BV shows promise as an addition to chemotherapy in GZL, even in the presence of severe liver impairment. The molecular pathogenesis of GZL is complex and heterogeneous, frequently involving aberrant NF-kB signaling and impaired apoptosis regulation via loss of TP53 expression. Understanding the underlying molecular mechanisms is essential for developing targeted therapies and identifying predictive biomarkers for treatment response.ConclusionThis case demonstrates the successful use of BV as a bridge to cytotoxic chemotherapy in a GZL patient with severe liver impairment, highlighting its potential safety and efficacy even in the setting of end-organ failure. Further investigation is warranted to define optimal treatment strategies, identify predictive biomarkers, and improve outcomes for patients with this rare and challenging lymphoma subtype.

show abstract

Section: Discussionmentioning

confidence: 99%

Brentuximab vedotin as a bridge to combination chemotherapy in gray zone lymphoma with severe liver impairment: a case report

Asrani,

Cengiz,

Petersen

et al. 2024

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“… 65 , 66 MDMX is involved in p53 signaling in anaplastic large cell lymphoma (ALCL). 67 In wt-p53 ALCL cells, MDMX pharmacological inhibition or siRNA-mediated MDMX silencing was associated with p53 signaling pathway activation, growth inhibition, and apoptotic cell death. Genomic aberration of MDMX has also been observed in salivary gland cancer (SGC) and high expression of MDMX was positively correlated with poor outcomes in patients.…”

Section: Phosphorylationmentioning

confidence: 92%

MDMX in Cancer: A Partner of p53 and a p53-Independent Effector

Lin,

Yan,

Huang

et al. 2024

BTT

View full text Add to dashboard Cite

The p53 tumor suppressor protein plays an important role in physiological and pathological processes. MDM2 and its homolog MDMX are the most important negative regulators of p53. Many studies have shown that MDMX promotes the growth of cancer cells by influencing the regulation of the downstream target gene of tumor suppressor p53. Studies have found that inhibiting the MDMX-p53 interaction can effectively restore the tumor suppressor activity of p53. MDMX has growth-promoting activities without p53 or in the presence of mutant p53. Therefore, it is extremely important to study the function of MDMX in tumorigenesis, progression and prognosis. This article mainly reviews the current research progress and mechanism on MDMX function, summarizes known MDMX inhibitors and provides new ideas for the development of more specific and effective MDMX inhibitors for cancer treatment.

show abstract

All activated signaling pathways lead to anaplastic large cell lymphoma (ALCL)

Bonzheim

Quintanilla-Martı́nez

2021

Leukemia & Lymphoma

View full text Add to dashboard Cite

MDMX/MDM4 is highly expressed and contributes to cell growth and survival in anaplastic large cell lymphoma

Cited by 3 publications

References 33 publications

Brentuximab vedotin as a bridge to combination chemotherapy in gray zone lymphoma with severe liver impairment: a case report

Brentuximab vedotin as a bridge to combination chemotherapy in gray zone lymphoma with severe liver impairment: a case report

MDMX in Cancer: A Partner of p53 and a p53-Independent Effector

All activated signaling pathways lead to anaplastic large cell lymphoma (ALCL)

Contact Info

Product

Resources

About