The Unique Immunophenotype of Double-Hit Lymphomas

Harrington, Alexandra M.; Olteanu, Horatiu; Kroft, Steven H.; Eshoa, Camellia

doi:10.1309/ajcpl11mahisijbq

Cited by 34 publications

(29 citation statements)

References 4 publications

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“…Many of the cases had one or more of the flow cytometric features of DHL that have been described previously 25-27 , including dim CD45, dim or absent CD20, and absent light chain expression. Our patients had similar clinical features as previously reported in DHL/THL 28,29 , including occurrence in predominantly older adults, most with extensive (stage IV) disease, and not uncommon CSF involvement.…”

Section: Discussionmentioning

confidence: 91%

Double- and triple-hit lymphomas can present with features suggestive of immaturity, including TdT expression, and create diagnostic challenges

Moench

Sachs

Aasen

et al. 2016

Leukemia & Lymphoma

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Double- and triple-hit lymphomas (DHL/THL) are aggressive B cell neoplasms characterized by translocation of MYC with concurrent BCL2 and/or BCL6 translocation. In this retrospective study from one institution, we report clinicopathologic features of 13 cases (9 DHL/4 THL). The median age was 59 years (range 30 to 74) and patients included 8 females and 5 males. Presentation included enlarging lymphadenopathy/masses (11 patients) and abnormal peripheral blood findings (2 patients). Features which raised the differential of an immature neoplasm included TdT positivity (4 cases, 2 THL/2 DHL); dim CD45 expression (7 cases), lack of CD20 (2 cases), or lack of surface immunoglobulin light chain (3 cases) by flow cytometry; and blastoid morphology (2 cases). We conclude that expression of TdT in a B cell lymphoma with mature features or expression of surface light chain in a case otherwise suggestive of B-lymphoblastic leukemia/lymphoma should prompt an expedited evaluation for DHL/THL.

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Section: Discussionmentioning

confidence: 91%

Double- and triple-hit lymphomas can present with features suggestive of immaturity, including TdT expression, and create diagnostic challenges

Moench

Sachs

Aasen

et al. 2016

Leukemia & Lymphoma

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“…14,20,47 Flow cytometric demonstration of dim CD20 and/or dim CD19 to help identify DHL has also been reported, but others find it to be of limited utility because most cases do not have these features. [48][49][50] But what about the role of MYC IHC? It has been reported that finding Ն70% MYCϩ cells had a sensitivity of 100% and specificity of 93% for a MYC break.…”

Section: What Are the Implications Associated Controversies And Ongmentioning

confidence: 99%

Diagnosis of ‘double hit’ diffuse large B-cell lymphoma and B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma: when and how, FISH versus IHC

2014

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“…Antibody-based therapies targeting CD20 using rituximab have significantly improved the general patient outcome in B-cell lymphoma patients, however “double-hit” lymphomas do not express or express much reduced levels of CD20 (11, 12). The development of more personalized and effective therapies including antibody based approaches for treating patients harboring “double-hit” lymphomas has been hampered by the lack of diagnostic awareness, therapeutic options and suitable pre-clinical models for therapeutic development.…”

Section: Introductionmentioning

confidence: 99%

Rapid generation of human B-cell lymphomas via combined expression of Myc and Bcl2 and their use as a preclinical model for biological therapies

et al. 2012

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While numerous mouse models of B cell malignancy have been developed via the enforced expression of defined oncogenic lesions, the feasibility of generating lineage-defined human B cell malignancies using mice reconstituted with modified human hematopoietic stem cells remains unclear. In fact, whether human cells can be transformed as readily as murine cells by simple oncogene combinations is a subject of considerable debate. Here, we describe the development of humanized mouse model of MYC/BCL2-driven “double-hit” lymphoma. By engrafting human hematopoietic stem cells transduced with the oncogene combination into immunodeficient mice, we generate a fatal B malignancy with complete penetrance. This humanized-MYC/BCL2-model (hMB) accurately recapitulates the histopathological and clinical aspects of steroid-, chemotherapy- and rituximab-resistant human “double-hit” lymphomas that involve the MYC and BCL2 loci. Notably, this model can serve as a platform for the evaluation of antibody-based therapeutics. As a proof of principle, we used this model to show that the anti-CD52 antibody alemtuzumab effectively eliminates lymphoma cells from the spleen, liver, and peripheral blood, but not from the brain. The hMB humanized mouse model underscores the synergy of MYC and BCL2 in “double-hit” lymphomas in human patients. Additionally, our findings highlight the utility of humanized mouse models in interrogating therapeutic approaches, particularly human-specific monoclonal antibodies.

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The Unique Immunophenotype of Double-Hit Lymphomas

Cited by 34 publications

References 4 publications

Double- and triple-hit lymphomas can present with features suggestive of immaturity, including TdT expression, and create diagnostic challenges

Double- and triple-hit lymphomas can present with features suggestive of immaturity, including TdT expression, and create diagnostic challenges

Diagnosis of ‘double hit’ diffuse large B-cell lymphoma and B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma: when and how, FISH versus IHC

Rapid generation of human B-cell lymphomas via combined expression of Myc and Bcl2 and their use as a preclinical model for biological therapies

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