Myc-mediated repression of microRNA-34a promotes high-grade transformation of B-cell lymphoma by dysregulation of FoxP1

Abstract Gastric marginal zone B-cell lymphoma of MALT type (MALT lymphoma) arises in the context of chronic inflammation induced by the bacterial pathogen Helicobacter pylori. Although generally considered an indolent disease, MALT lymphoma may transform to gastric diffuse large B-cell lymphoma (gDLBCL) through mechanisms that remain poorly understood. By comparing microRNA expression profiles of gastric MALT lymphoma and gDLBCL, we have identified a signature of 27 deregulated microRNAs(miRNAs) that share the characteristic of being transcriptionally repressed by Myc. Myc overexpression was consequently detected in 80% of gDLBCL but only 20% of MALT lymphomas spotted on a tissue microarray. A highly similar signature of Myc-repressed miRNAs was further detected in nodal DLBCL. Small interfering RNA–mediated knock-down of Myc blocked proliferation of DLBCL cell lines. Of the Myc-repressed miRNAs down-regulated in malignant lymphoma, miR-34a showed the strongest antiproliferative properties when overexpressed in DLBCL cells. We could further attribute miR-34a's tumor-suppressive effects to deregulation of its target FoxP1. FoxP1 overexpression was detected in gDLBCL but not in gastric MALT lymphoma; FoxP1 knock-down efficiently blocked DLBCL proliferation. In conclusion, our results elucidate a novel Myc- and FoxP1-dependent pathway of malignant transformation and suggest miR-34a replacement therapy as a promising strategy in lymphoma treatment.

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MALT lymphoma: epidemiology, clinical diagnosis and treatment

Journal of Medicine and Life ◽

10.25122/jml-2018-0035 ◽

2018 ◽

Vol 11 (3) ◽

pp. 187-193 ◽

Cited By ~ 13

Author(s):

Petruta Violeta Filip ◽

◽

Denisa Cuciureanu ◽

Laura Sorina Diaconu ◽

Ana Maria Vladareanu ◽

...

Keyword(s):

Helicobacter Pylori ◽

B Cell ◽

Malt Lymphoma ◽

Cell Lymphoma ◽

Gastric Lymphoma ◽

Eradication Therapy ◽

B Cell Lymphoma ◽

Gastric Malt Lymphoma ◽

H Pylori

Primary gastric lymphoma (PGL) represents a rare pathology, which can be easily misdiagnosed because of unspecific symptoms of the digestive tract. Histologically, PGL can vary from indolent marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) to aggressive diffuse large B-cell lymphoma (DLBCL). During the years, clinical trials revealed the important role of Helicobacter pylori (H. pylori) in the pathogenesis of gastric MALT lymphoma. Infection with Helicobacter pylori is an influential promoter of gastric lymphomagenesis initiation. Long-term studies revealed that eradication therapy could regress gastric lymphomas.

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High-grade malignant B-cell lymphoma of the retina in a patient with concomitant gastric MALT lymphoma

Graefe s Archive for Clinical and Experimental Ophthalmology ◽

10.1007/s00417-006-0364-9 ◽

2006 ◽

Vol 245 (3) ◽

pp. 448-450 ◽

Cited By ~ 4

Author(s):

Zaher H. Sbeity ◽

Sarah Coupland ◽

Karin U. Loeffler

Keyword(s):

B Cell ◽

Malt Lymphoma ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Gastric Malt Lymphoma ◽

High Grade

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Chemokine receptors in gastric MALT lymphoma: loss of CXCR4 and upregulation of CXCR7 is associated with progression to diffuse large B-cell lymphoma

Modern Pathology ◽

10.1038/modpathol.2012.134 ◽

2012 ◽

Vol 26 (2) ◽

pp. 182-194 ◽

Cited By ~ 39

Author(s):

Alexander JA Deutsch ◽

Elisabeth Steinbauer ◽

Nicole A Hofmann ◽

Dirk Strunk ◽

Tanja Gerlza ◽

...

Keyword(s):

B Cell ◽

Malt Lymphoma ◽

Chemokine Receptors ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Gastric Malt Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

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Helicobacter pylori cagA status and gastric mucosa-associated lymphoid tissue lymphoma: a systematic review and meta-analysis

Journal of Health Population and Nutrition ◽

10.1186/s41043-021-00280-9 ◽

2022 ◽

Vol 41 (1) ◽

Author(s):

Masoud Keikha ◽

Amirhossein Sahebkar ◽

Yoshio Yamaoka ◽

Mohsen Karbalaei

Keyword(s):

B Cell ◽

Malt Lymphoma ◽

Lymphoid Tissue ◽

Cell Lymphoma ◽

Meta Analysis ◽

B Cell Lymphoma ◽

Gastric Malt Lymphoma ◽

Large B Cell Lymphoma ◽

H Pylori

Abstract Background Recent studies have investigated the role of Helicobacter pylori infection in the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. It is estimated that approximately 0.1% of people infected with H. pylori develop gastric MALT lymphoma. However, the role of the CagA antigen, the highest causative agent of H. pylori, in increasing the risk of gastric MALT lymphoma remains unclear and controversial. A systematic review and meta-analysis were conducted to evaluate the effect of cagA status on the development of gastric MALT lymphoma. Methods All articles evaluating the status of the cagA gene in the development of gastric MALT lymphoma were collected using systematic searches in online databases, including PubMed, Scopus, Embase, and Google Scholar, regardless of publication date. The association between cagA and gastric MALT lymphoma was assessed using the odds ratio (OR) summary. In addition, a random-effects model was used in cases with significant heterogeneity. Results A total of 10 studies met our inclusion criteria, among which 1860 patients participated. No association between cagA status and the development of MALT lymphoma (extranodal marginal zone B-cell lymphoma) was found in this study (OR 1.30; 0.906–1.866 with 95% CIs; I2: 45.83; Q-value: 12.92). Surprisingly, a meaningful association was observed between cagA status and diffuse large B-cell lymphoma (OR 6.43; 2.45–16.84 with 95% CIs). We also observed an inverse association between vacA and gastric MALT lymphoma risk (OR 0.92; 0.57–1.50 with 95% CIs). Conclusions It seems that the infection with cagA-positive H. pylori strains does not have a meaningful effect on the gastric MALT lymphoma formation, while translocated CagA antigen into the B cells plays a crucial role in the development of diffuse large B-cell lymphoma.

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