PU.1 has previously been shown to be down-regulated in classical Hodgkin lymphoma (cHL) cells via promoter methylation. We performed bisulfite sequencing and proved that the promoter region and the -17 kb upstream regulatory element of the PU.1 gene were highly methylated. To evaluate whether down-regulation of PU.1 is essential for the growth of cHL cells, we conditionally expressed PU.1 in 2 cHL cell lines, L428 and KM-H2. Overexpression of PU.1 induced complete growth arrest and apoptosis in both cell lines. Furthermore, in a Hodgkin lymphoma tumor xenograft model using L428 and KM-H2 cell lines, overexpression of PU.1 led to tumor regression or stable disease. Lentiviral transduction of PU.1 into primary cHL cells also induced apoptosis. DNA microarray analysis revealed that among genes related to cell cycle and apoptosis, p21 (CDKN1A) was highly up-regulated in L428 cells after PU.1 induction. Stable knockdown of p21 rescued PU.1-induced growth arrest in L428 cells, suggesting that the growth arrest and apoptosis observed are at least partially dependent on p21 up-regulation. These data strongly suggest that PU.1 is a potent tumor suppressor in cHL and that induction of PU.1 with demethylation agents and/or histone deacetylase inhibitors is worth exploring as a possible therapeutic option for patients with cHL.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1182/blood-2012-05-431429 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Dynamic contrast enhanced MRI in nodal lymphoma: correlation of quantitative MR perfusion parameters with lymphoma subtype, Lugano stage and Ki-67 index.
Br J Radiol
January 2025
Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, 110029.
Background: Research into the intratumoral microenvironment in lymphoma has been escalated along with improved survival and new targeted therapies with an intent to refine risk stratification and prognostication. Various studies have reported significance of quantitative DCE-MRI parameters for predicting biological behaviour of various tumors. This study is an endeavour to supplement the existing literature on quantitative DCE-MRI in nodal lymphoma.
View Article and Find Full Text PDFUpregulation of CD19 by low-dose chidamide promotes CAR T cells functionality in B-cell non-Hodgkin lymphoma.
Discov Oncol
January 2025
Department of Hematology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
B-cell non-Hodgkin lymphoma (B-NHL) is a highly heterogeneous group of lymphopoietic malignancies that account for 85% to 90% of all non-Hodgkin lymphomas. In recent years, CD19 Chimeric antigen receptor T (CAR T) cell immunotherapy has significantly improved the cure rate of B-NHL patients, but there are still some patients who cannot achieve remission after treatment, or relapse after remission. Therefore, it is of great importance to overcome the drug resistance of CD19 CAR T cells after B-NHL treatment and reduce the recurrence rate of CD19 CAR T cells after B-NHL treatment.
View Article and Find Full Text PDFImpact of Comorbidities on Prognosis and Treatment Outcomes in Elderly Patients with Hodgkin Lymphoma.
Clin Pract
January 2025
Division of Haematology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.
: Hodgkin lymphoma (HL) primarily affects young adults, but about 20% of cases occur in patients over the age of 60 years. Older individuals often have comorbidities and poorer functional status, which can affect treatment choices. : We retrospectively analyzed data from HL patients over 60 years old who were treated at our institution between January 2010 and December 2023.
View Article and Find Full Text PDFSporadic Burkitt Lymphoma First Presenting as Painful Gingival Swellings and Tooth Hypermobility: A Life-Saving Referral.
Dent J (Basel)
December 2024
Department of Oral Medicine & Pathology and Hospital Dentistry, School of Dentistry, National and Kapodistrian University of Athens (NKUA), Greece 2 Thivon Street, 11527 Athens, Greece.
Burkitt lymphoma (BL) is an aggressive non-Hodgkin lymphoma (NHL), subdivided into endemic, sporadic, and immunodeficiency-associated forms. While jaw lesions are common in endemic BL, they are infrequent in sporadic cases, only rarely constituting the first manifestation of the disease. The aim of this study is to present a rare pediatric case of sporadic BL first manifesting as gingival swellings and tooth hypermobility and provide a review of all the published sporadic BL case reports as the first sign of disease.
View Article and Find Full Text PDFMinimal change disease following autologous stem cell transplant for Hodgkin lymphoma.
BMJ Case Rep
January 2025
Department of Haematology, Northern Health, Epping, Victoria, Australia.
Nephrotic syndrome is characterised by heavy proteinuria secondary to glomerular injury. It is an uncommon but serious complication of allogeneic haematopoietic stem cell transplant (HSCT), but rarely reported after autologous HSCT. Here, we report the case of a man in his mid-20s who presented with significant peripheral oedema 2 months after autologous HSCT for Hodgkin lymphoma.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!