Higher Incidence of B Cell Malignancies in Primary Immunodeficiencies: A Combination of Intrinsic Genomic Instability and Exocytosis Defects at the Immunological Synapse

Mastio, Jérôme; Saeed, Mezida B.; Wurzer, Hannah; Krecke, Max; Westerberg, Lisa S.; Thomas, Clément

doi:10.3389/fimmu.2020.581119

Cited by 7 publications

(5 citation statements)

References 315 publications

(375 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Various roles of WASp in innate and acquired immunity have been progressively reported, but the full function of WASp remains to be clarified (39)(40)(41)(42). Somatic reversion seems to occur frequently in WAS patients, as can be expected from the fact that at least 40 cases in 17 studies have been published to date (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36) (Table 1).…”

Section: Pids Associated With Reversion Mosaicism Wasmentioning

confidence: 99%

Reversion Mosaicism in Primary Immunodeficiency Diseases

Miyazawa

Wada

2021

Front. Immunol.

View full text Add to dashboard Cite

Reversion mosaicism has been reported in an increasing number of genetic disorders including primary immunodeficiency diseases. Several mechanisms can mediate somatic reversion of inherited mutations. Back mutations restore wild-type sequences, whereas second-site mutations result in compensatory changes. In addition, intragenic recombination, chromosomal deletions, and copy-neutral loss of heterozygosity have been demonstrated in mosaic individuals. Revertant cells that have regained wild-type function may be associated with milder disease phenotypes in some immunodeficient patients with reversion mosaicism. Revertant cells can also be responsible for immune dysregulation. Studies identifying a large variety of genetic changes in the same individual further support a frequent occurrence of reversion mosaicism in primary immunodeficiency diseases. This phenomenon also provides unique opportunities to evaluate the biological effects of restored gene expression in different cell lineages. In this paper, we review the recent findings of reversion mosaicism in primary immunodeficiency diseases and discuss its clinical implications.

show abstract

Section: Pids Associated With Reversion Mosaicism Wasmentioning

confidence: 99%

Reversion Mosaicism in Primary Immunodeficiency Diseases

Miyazawa

Wada

2021

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…WAS pro tein is crit i cal for actin cyto skel e tal rearrangement, which in turn is required for for ma tion of the immune syn apse in response to T, B, and NK cellcell sig nal ing, for reg u la tory Tcell func tion, mono cyte cyto kine pro duc tion, and lym pho cyte and den dritic cell shape and mobil ity. 24 Progressive CD8+ Tcell lymphopenia, impaired T cell receptor sig nal ing and acti va tion, poor NK cell func tion, over ac tive B cell receptor sig nal ing, and dysregulated mono cyte acti va tion all con spire to pro mote lymphomagenesis with and with out EBV infec tion (Figure 1).…”

Section: Individual Dis or Ders With More Than 1 Mech A Nism Involvedmentioning

confidence: 99%

How immunodeficiency can lead to malignancy

Lurain

Yarchoan

2021

Hematology

View full text Add to dashboard Cite

Immunodeficiency, whether acquired in the case of human immunodeficiency virus (HIV) infection or congenital due to inborn errors of immunity (IEIs), presents clinically with not only infection and immune dysregulation but also increased risk of malignancy. The range of malignancies seen is relatively limited and attributable to the particular cellular and molecular defects in each disease. CD4+ T-cell lymphopenia in people living with HIV infection (PLWH) and certain IEIs drive the predisposition to aggressive B-cell non-Hodgkin lymphomas, including certain rare subtypes rarely seen in immunocompetent individuals. PLWH and IEI that lead to profound T-cell lymphopenia or dysfunction also are at risk of cancers related to oncogenic viruses such as Kaposi sarcoma herpesvirus, Epstein-Barr virus, human papillomavirus (HPV), and Merkel cell polyomavirus. IEIs that affect natural killer cell development and/or function heavily predispose to HPV-associated epithelial cancers. Defects in DNA repair pathways compromise T- and B-lymphocyte development during immune receptor rearrangement in addition to affecting hematopoietic and epithelial DNA damage responses, resulting in both hematologic and nonhematologic cancers. Treatment of cancers in immunodeficient individuals should be curative in intent and pursued in close consultation with disease experts in immunology and infectious disease.

show abstract

“…Without tight regulation during B-cell development, cascade processes such as V(D)J recombination, somatic hypermutation (SHM), germinal center transit and clonal selection can contribute to malignant transformation of B cells at each step [33].…”

Section: Normal B-cell Developmentmentioning

confidence: 99%

Non-Coding RNAs in Normal B-Cell Development and in Mantle Cell Lymphoma: From Molecular Mechanism to Biomarker and Therapeutic Agent Potential

Kersy

Salmon‐Divon

Shpilberg

et al. 2021

IJMS

View full text Add to dashboard Cite

B-lymphocytes are essential for an efficient immune response against a variety of pathogens. A large fraction of hematologic malignancies are of B-cell origin, suggesting that the development and activation of B cells must be tightly regulated. In recent years, differentially expressed non-coding RNAs have been identified in mantle cell lymphoma (MCL) tumor samples as opposed to their naive, normal B-cell compartment. These aberrantly expressed molecules, specifically microRNAs (miRNAs), circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs), have a role in cellular growth and survival pathways in various biological models. Here, we provide an overview of current knowledge on the role of non-coding RNAs and their relevant targets in B-cell development, activation and malignant transformation, summarizing the current understanding of the role of aberrant expression of non-coding RNAs in MCL pathobiology with perspectives for clinical use.

show abstract

Higher Incidence of B Cell Malignancies in Primary Immunodeficiencies: A Combination of Intrinsic Genomic Instability and Exocytosis Defects at the Immunological Synapse

Cited by 7 publications

References 315 publications

Reversion Mosaicism in Primary Immunodeficiency Diseases

Reversion Mosaicism in Primary Immunodeficiency Diseases

How immunodeficiency can lead to malignancy

Non-Coding RNAs in Normal B-Cell Development and in Mantle Cell Lymphoma: From Molecular Mechanism to Biomarker and Therapeutic Agent Potential

Contact Info

Product

Resources

About