High expression of REV7 is an independent prognostic indicator in patients with diffuse large B-cell lymphoma treated with rituximab

Chromosomal translocation involving the BCL6 gene affects not only immunoglobulin (Ig) genes but also a number of non-Ig genes as partners. The molecular anatomy of the BCL6 gene rearrangements in 39 cases with diffuse large B-cell lymphoma (DLBCL) by long-distance polymerase chain reaction–based assays was determined. The results showed that Iggenes were affected in 21 cases; non-Ig genes, 15 cases; a deletion of more than a 1-kb segment, 2 cases; and a point mutation, 1 case. Comparative studies between the 21 cases withIg gene partners and the 17 cases with non-Iggene partners, including 2 cases with the deletion, showed that the overall survival of the latter group of patients was significantly inferior to that of the former (P = .0440), and the estimated 2-year overall survival rates were 58.3% vs 17.6% (P = .005). Non-Ig/BCL6 fusion is a poor prognostic indicator of DLBCL, and DLBCL with BCL6translocation could be subclassified according to the individual partner locus and/or gene.

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Circulating Exosomal MiR-107 Restrains Tumorigenesis in Diffuse Large B-Cell Lymphoma by Targeting 14-3-3η

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.667800 ◽

2021 ◽

Vol 9 ◽

Author(s):

Jiarui Liu ◽

Yang Han ◽

Shunfeng Hu ◽

Yiqing Cai ◽

Juan Yang ◽

...

Keyword(s):

B Cell ◽

Target Genes ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Prognostic Indicator ◽

Diagnostic Value ◽

Large B Cell Lymphoma ◽

Large B Cell

Exosomes, nanometer-sized membranous vesicles in body fluids, have emerged as promising non-invasive biomarkers for cancer diagnosis. However, the function of exosomes in diffuse large B-cell lymphoma (DLBCL) remains elusive. This study aimed to investigate the role of exosomal miR-107 in lymphomagenesis and explore its clinical significance. In this study, decreased exosomal miR-107, miR-375-3p, and upregulated exosomal miR-485-3p were detected in the plasma of DLBCL patients and showed potential diagnostic value. Downregulated miR-107 expression was associated with advanced Ann Arbor stage, high IPI score, LDH, and β2-MG level in DLBCL patients. Overexpression of miR-107 by miR-107 Agomir significantly abrogated cell proliferation, induced apoptosis, and inhibited cell invasion in vitro, and repressed tumor growth in vivo. Moreover, the downregulation of miR-107 went in the opposite direction. The target genes of miR-107 were mainly enriched in the PI3K-Akt, Hippo, and AMPK signaling pathways. Notably, upregulated 14-3-3η (YWHAH) was suppressed by miR-107 in DLBCL, suggesting that miR-107 may restrain tumorigenesis by targeting 14-3-3η. In summary, this study unveils the function of miR-107 in lymphomagenesis, highlighting its potential as a diagnostic and prognostic indicator and as a new therapeutic target in the management of DLBCL.

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CD163+ Tumor Associated Macrophages Predict Inferior Outcome in Patients with Diffuse Large B-Cell Lymphoma Treated with R-CHOP

Blood ◽

10.1182/blood.v126.23.5023.5023 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5023-5023

Author(s):

Hong Zeng ◽

Yongqiang Wei ◽

Muchen Xie ◽

Lei Yang ◽

Fen Huang ◽

...

Keyword(s):

Tumor Microenvironment ◽

B Cell ◽

Cell Lymphoma ◽

International Prognostic Index ◽

B Cell Lymphoma ◽

High Expression ◽

Tumor Associated Macrophages ◽

Large B Cell Lymphoma ◽

Cd163 Expression ◽

Large B Cell

Abstract Tumor-associated macrophages (TAMs), as the major component in tumor microenvironment, have been reported to correlate with the prognosis in diffuse large B-cell lymphoma (DLBCL). However due to the different subtypes of TAMs and the given therapy regimen, the prognostic value of TAMs in DLBCL patients remains controversial. To explore the prognostic significance of different TAMs subtypes in DLBCL patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone), we retrospectively analyzed 77 de novo DLBCL patients in present study. TAM markers including CD68 and CD163 were evaluated by immunohistochemistry. The cutoff value of CD68, CD163 and CD163/CD68 ratio was determined by receiver operating characteristic curve. In a total of 77 patients, CD68 high expression was found in71.4 %( 55/77) DLBCL patients and CD163 high expression in 51.4 %( 40/77 patients. Patients with high CD163 expression were more present with extranodal sites (P =0.049). However other clinical parameters including age, gender, Ann Arbor stage, performance stage, B symptoms, LDH and international prognostic index (IPI) showed no difference in patients with high and low CD68 or CD163 expression (P >0.05). CD68 expression has less effect on overall survival (OS) and event-free survival (EFS) (P =0.852, 0.782). However, high CD163 expression showed poor OS and EFS in DLBCL patients (P =0.006, 0.004) and also high CD163/CD68 ratio (P <0.001, 0.001). The multivariate analysis revealed that the high CD163 expression and CD163/CD68 ratio remained unfavorable factors for both OS (P =0.094, 0.002) and EFS (P =0.044, 0.016) independent of IPI. In conclusion, our date suggest that high CD163+ TAMs in tumor microenvironment may imply poor outcome in DLBCL patients treated with R-CHOP, but not CD68+ TAMs. Disclosures No relevant conflicts of interest to declare.

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HIGH EXPRESSION OF BCL-2 AND BCL-XL IN DIFFUSE LARGE B-CELL LYMPHOMA CONFER POOR PROGNOSIS BUT MAY BE REVERSIBLE BY COMBINED INHIBITION WITH BET INHIBITORS AND BH3 MIMETICS.

Hematological Oncology ◽

10.1002/hon.84_2629 ◽

2019 ◽

Vol 37 ◽

pp. 124-125

Author(s):

T.E. Cummin ◽

K. Cox ◽

T. Murray ◽

S. Barrans ◽

C. Sha ◽

...

Keyword(s):

B Cell ◽

Poor Prognosis ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

High Expression ◽

Bh3 Mimetics ◽

Large B Cell Lymphoma ◽

Bet Inhibitors ◽

Large B Cell

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ALDH1 Expression in Diffuse Large B-Cell Lymphoma: A Study of 88 Cases.

Blood ◽

10.1182/blood.v114.22.5019.5019 ◽

2009 ◽

Vol 114 (22) ◽

pp. 5019-5019

Author(s):

Ryan K. Olson ◽

Li Li ◽

C. E Sheehan ◽

Suzanne M. Homan ◽

Alida Hayner-Buchan ◽

...

Keyword(s):

Retinoic Acid ◽

Complete Remission ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Staining Intensity ◽

High Expression ◽

Large B Cell Lymphoma ◽

Aldh1 Expression ◽

Large B Cell

Abstract Abstract 5019 Introduction Diffuse large B-cell lymphoma (DLBCL) represents a heterogeneous category and tremendous effort has been made to identify sub-groups that are prognostically significant and to guide therapeutic decisions. Aldehyde dehydrogenase (ALDH) a family of ubiquitous enzymes throughout mammalian tissues catalyzes the oxidation of aldehydes to their corresponding carboxylic acids. Isoform 1 (ALDH1) plays a role in the biosynthesis of retinoic acid from Vitamin A. Retinoic acid is a regulator of cellular proliferation, differentiation and survival in normal human tissues. High expression of ALDH1 has been demonstrated in the putative cancer stem cells in malignancies of breast, lung, colon and other organs. Its expression has been associated with increased replicative potential, the ability to differentiate along multiple development lines, high tumorigenic potential and increased metastatic potential. However, more recently ALDH1 expression has been shown to correlate with favorable outcome in ovarian cancer. It has not been studied in DLBCL. The aim of the current study is to evaluate the expression of ALDH1 in DLBCL. Methods & Materials Formalin-fixed, paraffin embedded sections from 88 DLBCLs, were immunostained by automated methods (Ventana Medical Systems, Inc, Tucson, AZ) using monoclonal mouse anti-human ALDH antibody (Clone: 44/ALDH; Immunogen: Human ALDH1, aa 7 – 128; BD Transduction Laboratories). Cytoplasmic immunoreactivity was semi quantitatively assessed in all cases. Scoring was based on staining intensity (weak, moderate, intense) and percentage of positive cells (focal <= 25%, regional 26-50%, diffuse >50%). Results were correlated with clinicopathologic variables. Results High expression of ALDH1 was observed in 26/88 (30%) cases of DLBCL. The staining intensity and distribution pattern varied somewhat by outcome data. Remission status was known in 23 patients. 18 patients achieved complete remission. Interestingly, all 7 patients with high expression of ALDH1 achieved complete remission (p= 0.095). Recurrence information was known in 87 patients. High expression of ALDH1 was seen in 26 cases. Only one of these patients recurred (p=0.19). No association was seen with stage, HIV status, survival or age. Conclusion We have demonstrated that ALDH1 is expressed in DLBCL. Moreover, cases with high expression of ALDH1 trend towards complete remission and lack of recurrence. Further studies of ALDH1 expression in DLBCL appear warranted, potentially defining prognostically relevant sub-groups. Disclosures No relevant conflicts of interest to declare.

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