Composite Lymphomas And The Relationship Of Hodgkin Lymphoma To Non-Hodgkin Lymphomas
M. Weniger, R. Küppers
Published 2018 · Biology
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Composite lymphomas are rare combinations of two distinct types of lymphomas occurring simultaneously in one patient, often a Hodgkin lymphoma (HL) and a non-Hodgkin lymphoma (NHL). In other instances, a HL and a NHL may occur subsequently in a patient. Some composite lymphomas likely represent chance occurrences of two independent tumors. However, in a large fraction of combined HL and NHL, the two lymphomas are clonally related and hence have a common origin. Detailed analysis of the rearranged immunoglobulin V region genes of such related lymphomas provided strong evidence that in many cases, the two lymphomas in composite as well as consecutive HL and B-cell NHL developed from distinct daughter cells of a mutating germinal center (GC) B-cell clone. Clonally related composite lymphomas carry both shared early genetic lesions as well as later separate transforming events, supporting a multi-step transformation process in such cases. The pattern of clonally related immunoglobulin V region genes and shared genetic lesions points to a close relationship of HL to B-cell NHL.
This paper references
Pathogenesis of human B cell lymphomas.
A. Shaffer (2012)
Tracing B cell development in human germinal centres by molecular analysis of single cells picked from histological sections.
R. Küppers (1993)
Composite lymphoma of nodular lymphocyte-predominant and classical Hodgkin lymphoma-Epstein-Barr virus association suggests divergent pathogenesis despite clonal relatedness.
M. Szczepanowski (2013)
PD-1-PD-1 ligand interaction contributes to immunosuppressive microenvironment of Hodgkin lymphoma.
R. Yamamoto (2008)
Distinct Clonal Origin in Two Cases of Hodgkin’s Lymphoma Variant of Richter’s Syndrome Associated With EBV Infection
L. de Leval (2004)
Epigenetic processes play a major role in B-cell-specific gene silencing in classical Hodgkin lymphoma.
A. Ushmorov (2006)
Germinal Center Founder Cells Display Propensity for Apoptosis before Onset of Somatic Mutation
S. Lebecque (1997)
Gene expression profiling of isolated tumour cells from anaplastic large cell lymphomas: insights into its cellular origin, pathogenesis and relation to Hodgkin lymphoma
Susan Eckerle (2009)
Constitutive activation of phosphatidyl-inositide 3 kinase contributes to the survival of Hodgkin's lymphoma cells through a mechanism involving Akt kinase and mTOR.
A. Dutton (2005)
Primary mediastinal (thymic) B-cell lymphoma is characterized by gains of chromosomal material including 9p and amplification of the REL gene.
S. Joos (1996)
Analyzing primary Hodgkin and Reed-Sternberg cells to capture the molecular and cellular pathogenesis of classical Hodgkin lymphoma.
E. Tiacci (2012)
Recurrent mutations of the exportin 1 gene (XPO1) and their impact on selective inhibitor of nuclear export compounds sensitivity in primary mediastinal B‐cell lymphoma
F. Jardin (2016)
Aberrant expression of Notch1 interferes with the B-lymphoid phenotype of neoplastic B cells in classical Hodgkin lymphoma
F. Jundt (2008)
Primary mediastinal B-cell lymphoma: high frequency of BCL-6 mutations and consistent expression of the transcription factors OCT-2, BOB.1, and PU.1 in the absence of immunoglobulins.
S. Pileri (2003)
cDNA arrays: gene expression profiles of Hodgkin's disease and anaplastic large cell lymphoma cell lines.
C. Thorns (2002)
Inactivating I kappa B epsilon mutations in Hodgkin/Reed-Sternberg cells.
F. Emmerich (2003)
The oncoprotein NPM-ALK of anaplastic large-cell lymphoma induces JUNB transcription via ERK1/2 and JunB translation via mTOR signaling.
P. Staber (2007)
Expression of activation-induced cytidine deaminase is confined to B-cell non-Hodgkin's lymphomas of germinal-center phenotype.
L. Smit (2003)
Chromosomal rearrangements involving the BCL3 locus are recurrent in classical Hodgkin and peripheral T-cell lymphoma.
J. Martín-Subero (2006)
The oncogenic JUNB/CD30 axis contributes to cell cycle deregulation in ALK+ anaplastic large cell lymphoma
Vassilis Atsaves (2014)
Molecular characterization of primary mediastinal B cell lymphoma.
P. Tsang (1996)
Clonally related splenic marginal zone lymphoma and Hodgkin lymphoma with unmutated V gene rearrangements and a 15‐yr time gap between diagnoses
R. Rosenquist (2004)
miR-135b mediates NPM-ALK-driven oncogenicity and renders IL-17-producing immunophenotype to anaplastic large cell lymphoma.
H. Matsuyama (2011)
Classical Hodgkin's disease and follicular lymphoma originating from the same germinal center B cell.
T. Marafioti (1999)
Detection of clonal T-cell receptor gamma-chain gene rearrangements in Reed-Sternberg cells of classic Hodgkin disease.
V. Seitz (2000)
Acquired initiating mutations in early hematopoietic cells of CLL patients.
F. Damm (2014)
Pathogenesis of classical and lymphocyte-predominant Hodgkin lymphoma.
R. Schmitz (2009)
The 2016 revision of the World Health Organization classification of lymphoid neoplasms.
S. Swerdlow (2016)
Differential expression of activation-induced cytidine deaminase (AID) in nodular lymphocyte-predominant and classical Hodgkin lymphoma.
A. Greiner (2005)
Inhibition of the phosphatidylinositol‐3 kinase/Akt promotes G1 cell cycle arrest and apoptosis in Hodgkin lymphoma
G. Georgakis (2006)
Composite Hodgkin Lymphoma and Mantle Cell Lymphoma: Two Clonally Unrelated Tumors
A. Caleo (2003)
MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers
C. Steidl (2011)
The clonal relationship between nodular sclerosis Hodgkin's disease with a clonal Reed-Sternberg cell population and a subsequent B-cell small noncleaved cell lymphoma.
T. Ohno (1998)
Detection and prognostic value of recurrent exportin 1 mutations in tumor and cell-free circulating DNA of patients with classical Hodgkin lymphoma
V. Camus (2016)
Recurrent somatic mutations of PTPN1 in primary mediastinal B cell lymphoma and Hodgkin lymphoma
J. Gunawardana (2014)
Stat3 is required for ALK-mediated lymphomagenesis and provides a possible therapeutic target
R. Chiarle (2005)
The biology of Hodgkin's lymphoma
R. Küppers (2009)
Translocation t(2;5) is not a primary event in Hodgkin's disease. Simultaneous immunophenotyping and interphase cytogenetics.
K. Weber-Matthiesen (1996)
Clonal relation in a case of CLL, ALCL, and Hodgkin composite lymphoma.
A. van den Berg (2002)
The oncogenic transcription factor IRF4 is regulated by a novel CD30/NF-κB positive feedback loop in peripheral T-cell lymphoma.
Rebecca L. Boddicker (2015)
Hodgkin transformation of small lymphocytic lymphoma: gene usage, mutational status and clonal relationship
L. Venkatraman (2007)
Clinicopathological features of classical Hodgkin lymphoma in patients ≥ 40 years old, with special reference to composite cases.
A. Maeshima (2015)
Hodgkin and Reed-Sternberg cells in Hodgkin's disease represent the outgrowth of a dominant tumor clone derived from (crippled) germinal center B cells
H. Kanzler (1996)
Intrinsic inhibition of transcription factor E2A by HLH proteins ABF-1 and Id2 mediates reprogramming of neoplastic B cells in Hodgkin lymphoma
S. Mathas (2006)
Recurrent involvement of the REL and BCL11A loci in classical Hodgkin lymphoma.
J. Martín-Subero (2002)
Derepression of an endogenous long terminal repeat activates the CSF1R proto-oncogene in human lymphoma
B. Lamprecht (2010)
Common features and differences in the transcriptome of large cell anaplastic lymphoma and classical Hodgkin's lymphoma.
K. Willenbrock (2006)
Common Germinal-Center B-Cell Origin of the Malignant Cells in Two Composite Lymphomas, Involving Classical Hodgkin’s Disease and Either Follicular Lymphoma or B-CLL
R. Küppers (2001)
Comprehensive characterization of programmed death ligand structural rearrangements in B-cell non-Hodgkin lymphomas.
L. Chong (2016)
Sequential Development of Hodgkin's Disease and CD30+ Diffuse Large B-Cell Lymphoma in a Patient With MALT-Type Lymphoma: Evidence of Different Clonal Origin of Single Microdissected Reed-Sternberg Cells
M. Parrens (2002)
Composite recurrent hodgkin lymphoma and diffuse large B-cell lymphoma: one clone, two faces.
Q. Huang (2006)
B cells under influence: transformation of B cells by Epstein–Barr virus
R. Küppers (2003)
Immunoglobulin Gene Rearrangement Analysis in Composite Hodgkin Disease and Large B-Cell Lymphoma: Evidence for Receptor Revision of Immunoglobulin Heavy Chain Variable Region Genes in Hodgkin-Reed-Sternberg Cells?
C. Bellan (2002)
Genomic Alterations in CIITA Are Frequent in Primary Mediastinal Large B Cell Lymphoma and Are Associated with Diminished MHC Class II Expression.
A. Mottok (2015)
AP1-Dependent Galectin-1 Expression Delineates Classical Hodgkin and Anaplastic Large Cell Lymphomas from Other Lymphoid Malignancies with Shared Molecular Features
S. Rodig (2008)
Hodgkin's disease, lymphomatoid papulosis, and cutaneous T-cell lymphoma derived from a common T-cell clone.
T. H. Davis (1992)
Mediastinal (thymic) large B-cell lymphoma: where do we stand?
T. Barth (2002)
High frequency of t(14;18) in Hodgkin's lymphoma associated with follicular lymphoma.
Maki Yoshida (2012)
Clonal identity of nodular lymphocyte-predominant Hodgkin's disease and T-cell-rich B-cell lymphoma.
S. Shimodaira (2000)
Hodgkin's disease variant of Richter's syndrome in chronic lymphocytic leukaemia patients previously treated with fludarabine
D. Fong (2005)
Deep sequencing reveals lack of a clonal relationship between a metachronous classical hodgkin and diffuse large B-cell lymphoma.
I. Siddiqi (2014)
Mechanisms of B-cell lymphoma pathogenesis
R. Küppers (2005)
Composite Lymphoma: EBV-positive Classic Hodgkin Lymphoma and Peripheral T-cell Lymphoma: A Case Report
Gabriela Gualco (2009)
TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis.
Cyril Quivoron (2011)
Identification of common germinal-center B-cell precursors in two patients with both Hodgkin's disease and non-Hodgkin's lymphoma.
A. Braeuninger (1999)
T-Cell Variant of Classical Hodgkin's Lymphoma with Nodal and Cutaneous Manifestations Demonstrated by Single-Cell Polymerase Chain Reaction
K. Willenbrock (2002)
Hodgkin and Reed-Sternberg cells in lymphocyte predominant Hodgkin disease represent clonal populations of germinal center-derived tumor B cells.
A. Braeuninger (1997)
Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma.
R. Crescenzo (2015)
Genomic imbalances including amplification of the tyrosine kinase gene JAK2 in CD30+ Hodgkin cells.
S. Joos (2000)
Gene deregulation and spatial genome reorganization near breakpoints prior to formation of translocations in anaplastic large cell lymphoma
S. Mathas (2009)
The AP1-dependent secretion of galectin-1 by Reed–Sternberg cells fosters immune privilege in classical Hodgkin lymphoma
Przemysław Juszczyński (2007)
Single-cell analysis of the t(14;18)(q32;q21) chromosomal translocation in Hodgkin's disease demonstrates the absence of this translocation in neoplastic Hodgkin and Reed-Sternberg cells.
S. Gravel (1998)
BCL2 and BCL3 are recurrent translocation partners of the IGH locus.
Natalia Szymanowska (2008)
Rare Occurrence of Classical Hodgkin's Disease as a T Cell Lymphoma
M. Müschen (2000)
Down-regulation of BOB.1/OBF.1 and Oct2 in classical Hodgkin disease but not in lymphocyte predominant Hodgkin disease correlates with immunoglobulin transcription.
H. Stein (2001)
IL-21 contributes to JAK3/STAT3 activation and promotes cell growth in ALK-positive anaplastic large cell lymphoma.
J. Dien Bard (2009)
Molecular Diagnosis of Primary Mediastinal B Cell Lymphoma Identifies a Clinically Favorable Subgroup of Diffuse Large B Cell Lymphoma Related to Hodgkin Lymphoma
A. Rosenwald (2003)
Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma.
M. Green (2010)
Subclonal evolution of a classical Hodgkin lymphoma from a germinal center B‐cell‐derived mantle cell lymphoma
S. Schneider (2014)
Highly recurrent mutations of SGK1, DUSP2 and JUNB in nodular lymphocyte predominant Hodgkin lymphoma
S. Hartmann (2016)
Classical Hodgkin lymphoma is characterized by high constitutive expression of activating transcription factor 3 (ATF3), which promotes viability of Hodgkin/Reed-Sternberg cells.
M. Janz (2006)
Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas
L. Pasqualucci (2001)
Elevated NF-κB p50 complex formation and Bcl-3 expression in classical Hodgkin, anaplastic large-cell, and other peripheral T-cell lymphomas
S. Mathas (2005)
Loss of the B-lineage-specific gene expression program in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma.
I. Schwering (2003)
Demonstration of chimeric DNA of bcl-2 and immunoglobulin heavy chain in follicular lymphoma and subsequent Hodgkin lymphoma from the same patient.
Naoya Nakamura (2007)
Composite Blastoid Variant of Mantle Cell Lymphoma and Classical Hodgkin Lymphoma
C. Murray (2017)
Pathobiology of Anaplastic Large Cell Lymphoma
P. Piccaluga (2010)
Essential role of IRF4 and MYC signaling for survival of anaplastic large cell lymphoma.
André Weilemann (2015)
TP53 gene mutations in Hodgkin lymphoma are infrequent and not associated with absence of Epstein‐Barr virus
E. Maggio (2001)
Aberrant somatic hypermutation in tumor cells of nodular-lymphocyte-predominant and classic Hodgkin lymphoma.
A. Liso (2006)
A common B-cell precursor in composite lymphomas.
K. Kerl (1999)
Pathogenesis, diagnosis, and treatment of composite lymphomas.
R. Küppers (2014)
Expression status of BCL-6 and syndecan-1 identifies distinct histogenetic subtypes of Hodgkin's disease.
A. Carbone (1998)
An unusual variant of composite lymphoma: a short case report and review of the literature.
S. Thirumala (2000)
Clonal Deleterious Mutations in the Iκbα Gene in the Malignant Cells in Hodgkin's Lymphoma
B. Jungnickel (2000)
Constitutive AP-1 Activity and EBV Infection Induce PD-L1 in Hodgkin Lymphomas and Posttransplant Lymphoproliferative Disorders: Implications for Targeted Therapy
M. Green (2012)
Lack of IKBA coding region mutations in primary mediastinal large B-cell lymphoma and the host response subtype of diffuse large B-cell lymphoma.
H. Takahashi (2006)
Aberrant somatic hypermutation in primary mediastinal large B-cell lymphoma
D. Rossi (2005)
Activated Notch1 signaling promotes tumor cell proliferation and survival in Hodgkin and anaplastic large cell lymphoma.
F. Jundt (2002)
TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma
R. Schmitz (2009)
Cooperative epigenetic modulation by cancer amplicon genes.
L. Rui (2010)
The origin of Hodgkin and Reed/Sternberg cells in Hodgkin's disease.
R. Küppers (1998)
Analysis of a Clonally Related Mantle Cell and Hodgkin Lymphoma Indicates Epstein-Barr Virus Infection of a Hodgkin/Reed-Sternberg Cell Precursor in a Germinal Center
M. Tinguely (2003)
Frequent expression of the B-cell-specific activator protein in Reed-Sternberg cells of classical Hodgkin's disease provides further evidence for its B-cell origin.
H. Foss (1999)
Mediastinal Gray Zone Lymphoma: The Missing Link Between Classic Hodgkin's Lymphoma and Mediastinal Large B-Cell Lymphoma
Alexandra Traverse-Glehen (2005)
[Biallelic mutation of SOCS-1 impairs JAK2 degradation and sustains phospho-JAK2 action in MedB-1 mediastinal lymphoma line].
T. Barth (2005)
Indications for peripheral light-chain revision and somatic hypermutation without a functional B-cell receptor in precursors of a composite diffuse large B-cell and Hodgkin's lymphoma
R. Rosenquist (2004)
Clonal evolution of a follicular lymphoma: evidence for antigen selection.
D. Bahler (1992)
PTEN and p27 expression in mature T-cell and NK-cell neoplasms
A. Üner (2005)
Genomic rearrangements involving programmed death ligands are recurrent in primary mediastinal large B-cell lymphoma.
David D W Twa (2014)
Pathogenesis of follicular lymphoma.
Robert Kridel (2012)
Hodgkin's disease, lymphocytic predominance nodular. Increased risk for subsequent non‐Hodgkin's lymphomas
M. Miettinen (1983)
Lymphoma Heterogeneity: Three Different Histological Pictures and One Unique Clone
Sara Alonso-Álvarez (2016)
JunB expression is a common feature of CD30+ lymphomas and lymphomatoid papulosis
G. Rassidakis (2005)
Repeated Clonal Relapses in Classical Hodgkin's Lymphoma and the Occurrence of a Clonally Unrelated Diffuse Large B Cell Non-Hodgkin Lymphoma in the Same Patient
Roman K. Thomas (2004)
Origin and pathogenesis of nodular lymphocyte–predominant Hodgkin lymphoma as revealed by global gene expression analysis
V. Brune (2008)
Gains of 2p involving the REL locus correlate with nuclear c-Rel protein accumulation in neoplastic cells of classical Hodgkin lymphoma.
T. Barth (2003)
Overexpression of I kappa B alpha without inhibition of NF-kappaB activity and mutations in the I kappa B alpha gene in Reed-Sternberg cells.
F. Emmerich (1999)
Class switch recombination was specifically targeted to immunoglobulin (Ig)G4 or IgA in Hodgkin's disease‐derived cell lines
J. Irsch (2001)
Transcription factor B-cell-specific activator protein (BSAP) is differentially expressed in B cells and in subsets of B-cell lymphomas.
L. Krenács (1998)
Composite lymphoma with diffuse large B-cell lymphoma and classical Hodgkin lymphoma components: A case report and review of the literature.
G. Goyal (2016)
Patterned CpG methylation of silenced B cell gene promoters in classical Hodgkin lymphoma-derived and primary effusion lymphoma cell lines.
J. R. Doerr (2005)
Epigenetic silencing of the immunoglobulin heavy-chain gene in classical Hodgkin lymphoma-derived cell lines contributes to the loss of immunoglobulin expression.
A. Ushmorov (2004)
Gray zone lymphoma: chromosomal aberrations with immunophenotypic and clinical correlations
F. Eberle (2011)
Nodular paragranuloma can transform into high-grade malignant lymphoma of B type.
M. Hansmann (1989)
Expression pattern of MUM1/IRF4 in the spectrum of pathology of Hodgkin's disease
A. Carbone (2002)
Mechanisms of chromosomal translocations in B cell lymphomas
R. Küppers (2001)
Chromosomal breakpoints affecting immunoglobulin loci are recurrent in Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma.
J. Martín-Subero (2006)
Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma.
L. Mansouri (2016)
NPM-ALK oncogenic kinase promotes cell-cycle progression through activation of JNK/cJun signaling in anaplastic large-cell lymphoma.
V. Leventaki (2007)
IgVH Mutational Status and Clonality Analysis of Richter's Transformation: Diffuse Large B-cell Lymphoma and Hodgkin Lymphoma in Association With B-cell Chronic Lymphocytic Leukemia (B-CLL) Represent 2 Different Pathways of Disease Evolution
Zhengrong Mao (2007)
Insights into the multistep transformation process of lymphomas: IgH-associated translocations and tumor suppressor gene mutations in clonally related composite Hodgkin's and non-Hodgkin's lymphomas
R. Schmitz (2005)
Origin of nodular lymphocyte-predominant Hodgkin's disease from a clonal expansion of highly mutated germinal-center B cells.
T. Marafioti (1997)
Aberrantly expressed c‐Jun and JunB are a hallmark of Hodgkin lymphoma cells, stimulate proliferation and synergize with NF‐κB
S. Mathas (2002)
Hematopoietic Stem Cell Origin of BRAFV600E Mutations in Hairy Cell Leukemia
S. S. Chung (2014)
Molecular features of primary mediastinal B‐cell lymphoma: involvement of p16INK4A, p53 and c‐myc
A. Scarpa (1999)
Mutation of the p53 gene is not a typical feature of Hodgkin and Reed-Sternberg cells in Hodgkin's disease.
M. Montesinos-Rongen (1999)
Thymic B Cells Are Licensed to Present Self Antigens for Central T Cell Tolerance Induction.
T. Yamano (2015)
Germinal centres: role in B-cell physiology and malignancy
U. Klein (2008)
Isotype-switched immunoglobulin genes with a high load of somatic hypermutation and lack of ongoing mutational activity are prevalent in mediastinal B-cell lymphoma.
F. Leithäuser (2001)
c-Jun Expression and Activation are Restricted to CD30+ Lymphoproliferative Disorders
E. Drakos (2007)
Mutations of the tumor suppressor gene SOCS-1 in classical Hodgkin lymphoma are frequent and associated with nuclear phospho-STAT5 accumulation
M. Weniger (2006)
Three coexisting lymphomas in one patient: genetically related or only a coincidence?
M. Steinhoff (2006)
The importance of Notch signaling in peripheral T-cell lymphomas
Maria R Kamstrup (2014)
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