Clonal relation in a case of CLL, ALCL, and Hodgkin composite lymphoma

Berg, Anke van den; Maggio, Ewerton Marques; Rust, Renata; Kooistra, Klaas; Diepstra, Arjan; Poppema, Sibrand

doi:10.1182/blood.v100.4.1425.h81602001425_1425_1429

Cited by 77 publications

(39 citation statements)

References 20 publications

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“…Histologically, the two lymphoma populations, although exhibiting a markedly different morphology and immunophenotype, were intermingled to a degree not seen in the previous CL. [3][4][5][6][7][8]28,29 In particular, at a first glance this case appeared as a cHL of the lymphocyte-rich subtype, 39 because typical HRS cells (sometimes rosetted by T cells) were embedded in a somewhat nodular cellular background composed of apparently normal, expanded mantle zones. It was only after performing a cyclin D1 staining (prompted by the clinical history of the patient) that the neoplastic nature of the mantle zone B cells became evident.…”

Section: Discussionmentioning

confidence: 93%

“…5 For mutation analysis, samples after WGA of both lymphoma types were used. 6 The NOTCH1 analysis consistently detected a known single nucleotide polymorphism (rs2229974) at DNA position 53603 of NG_007458.1 with homozygous genotype (T/T) in exon 34. 7 Likely occurred independently in the HRS and MCL cells.…”

Section: Cdkn2a-b/9p21mentioning

confidence: 93%

“…1,2 Often, CL show a clonal relationship. [3][4][5][6][7][8] In most cases analyzed, the immunoglobulin (Ig) V genes of the two lymphoma entities carried both shared and distinct somatic mutations. This suggests that the common precursor of the two lymphomas underwent a germinal center (GC) reaction, where somatic hypermutation of IgV genes takes place 9 (explaining the shared mutations), and that the two lymphomas then developed from different members of the progeny of this common precursor (explaining the distinct mutations).Classical HL (cHL) is characterized by the occurrence of rare Hodgkin and Reed/Sternberg (HRS) tumor cells embedded in a mixed cellular infiltrate.…”

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confidence: 99%

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Subclonal evolution of a classical Hodgkin lymphoma from a germinal center B‐cell‐derived mantle cell lymphoma

Schneider

Crescenzi

Schneider

et al. 2013

Intl Journal of Cancer

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Composite lymphomas (CL) represent the occurrence of two distinct lymphomas in the same patient. Often, CL share a common cellular origin, thus representing a unique model to investigate the multistep genetic path leading to lymphomagenesis in general and to the specific development of each distinct lymphoma component in particular. Here, we present the molecular analysis of a case consisting of an unusual Hodgkin lymphoma (HL) and a mantle cell lymphoma (MCL), intimately admixed within one another in lymph nodes and bone marrow yet phenotypically distinct, in a patient who first presented with splenic/leukemic MCL two years earlier. MCL and Hodgkin and Reed/Sternberg (HRS) cells harbored identical immunoglobulin (Ig) V H gene rearrangements with shared somatic mutations, proving their common clonal origin from a (post-)germinal center (GC) B cell. This also demonstrates the (post-)GC origin of MCL with mutated IgV genes. Both lymphomas carried the same CCND1/IGH translocation and, unexpectedly for HL, expressed cyclin D1 and OCT2. Thus, HRS cells are able to preserve IGH locus activity (otherwise usually silenced in HL) to promote expression of an oncogene translocated into this locus. Both lymphoma populations further showed an identical TP53 function-impairing mutation, and later acquired a TP53 heterozygous deletion independently from one another (convergent evolution). The surprisingly close genetic relationship of the lymphomas, together with their histological intermingling and the clinical history of the patient, suggests subclonal evolution of HL from MCL as a plausible pathway in alternative to that so far described in CL, i.e. separate development from a common precursor.A composite lymphoma (CL) is defined by the simultaneous or sequential presence of two distinct types of lymphomas, e.g. a B-cell non-Hodgkin lymphoma (NHL) and a Hodgkin lymphoma (HL) or two different NHL, in the same patient. 1,2Often, CL show a clonal relationship. [3][4][5][6][7][8] In most cases analyzed, the immunoglobulin (Ig) V genes of the two lymphoma entities carried both shared and distinct somatic mutations. This suggests that the common precursor of the two lymphomas underwent a germinal center (GC) reaction, where somatic hypermutation of IgV genes takes place 9 (explaining the shared mutations), and that the two lymphomas then developed from different members of the progeny of this common precursor (explaining the distinct mutations).Classical HL (cHL) is characterized by the occurrence of rare Hodgkin and Reed/Sternberg (HRS) tumor cells embedded in a mixed cellular infiltrate. HRS cells mostly derive from GC B cells. 10,11 The signaling pathways NF-jB and

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Section: Discussionmentioning

confidence: 93%

Section: Cdkn2a-b/9p21mentioning

confidence: 93%

mentioning

confidence: 99%

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Subclonal evolution of a classical Hodgkin lymphoma from a germinal center B‐cell‐derived mantle cell lymphoma

Schneider

Crescenzi

Schneider

et al. 2013

Intl Journal of Cancer

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“…into the development of those composite lymphomas were provided by single cell PCR analysis for rearrranged Ig V genes of the two lymphomas. Thus, clonal relationship between the two different tumours was demonstrated in the majority of the cases analysed (13)(14)(15)(16)(17)(18)(19)(20). Interestingly, in many of the clonally related cases, the rearranged V genes of the two lymphomas showed both shared as well as distinct somatic mutations in the HRS and the NHL cells.…”

Section: Pathogenesis Of Composite Lymphomasmentioning

confidence: 92%

Pathogenesis of Hodgkin's lymphoma

Küppers

Schmitz

Distler

et al. 2005

European J of Haematology

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In Hodgkin's lymphoma (HL), the B cell origin of the tumour cells, the Hodgkin and Reed‐Sternberg (HRS) cells, has been disclosed by molecular single cell analysis about 10 yr ago. This finding formed the basis for various studies aimed to better understand the pathogenesis of this peculiar malignancy and the pathophysiology of the HRS cells. Work of our groups in this regard was focussed recently on two main topics, namely the study of differential gene expression in HRS cells and the pathogenesis of composite lymphomas. Composite lymphomas are combinations of HL and B cell non‐Hodgkin lymphomas, that turned out to be often clonally related. By molecular analysis of several composite lymphomas for potential transforming events, we identified examples of both shared as well as distinct transforming events. Comparing gene expression profiles of HL‐derived cell lines with the corresponding profiles from other B cell lymphomas and normal B cell subsets revealed a global down‐regulation of the B cell‐specific gene expression signature in HRS cells. Moreover, we identifed aberrant expression and activity of multiple receptor tyrosine kinases in HRS cells of classical and to a lesser extend lymphocyte predominant HL, which appears to be a unique feature of HL, and may offer novel strategies for treatment.

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“…Molecular analysis of rare cases of bigenotypic and biphenotypic, t(14;18)-positive lymphomas showed that two distinct neoplastic B-cell clones may be derived from a single progenitor cell (Cleary et al, 1988). Another study of a composite lymphoma also revealed a common genetic abnormality that was found in three different lymphomatous components (van de Berg et al, 2002). The presence of a dormant lymphoma progenitor cell may explain why FL, a (2006) reported on the molecular characterisation of a large number of patients suffering from pyruvate kinase (PK) deficiency.…”

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confidence: 99%