<i>MYC</i> or <i>BCL2</i> copy number aberration is a strong predictor of outcome in patients with diffuse large B-cell lymphoma

Lu, Ting; Fan, Lei; Wang, Li; Wu, Jack; Miao, Kou Rong; Liang, Jin; Gong, Qixing; Wang, Zhen; Young, Ken H.; Xu, Wei; Zhang, Zhi Hong; Li, Jian Yong

doi:10.18632/oncotarget.4073

Cited by 49 publications

(46 citation statements)

References 35 publications

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“…The most frequently observed derangement leading to MYC protein overexpression involves the translocation of MYC to the immunoglobulin gene (IG) locus. [22][23][24][25][26] The MYC-IG rearrangement is the hallmark of BL and serves as a defining characteristic in approximately 60% of HGBL cases and in a minority of cases of DLBCL.…”

Section: Mycmentioning

confidence: 99%

“…[18][19][20][21] Finally, MYC gene amplification has been noted in approximately 2% to 20% of DLBCL cases, although the impact on the MYC protein expression levels and prognosis is unclear, with discordant findings in the literature. [22][23][24][25][26]…”

Section: Mycmentioning

confidence: 99%

“…30,36,37 An increased MYC copy number or gene amplification can also occur in 8% to 20% of DLBCL cases, although its impact on prognosis is less clear. 22,23,38 Landsburg et al 26 double-or triple-hit phenotype. In summary, data suggest that MYC amplification may be associated with inferior outcomes in DLBCL; however, further studies are needed to more fully evaluate its prognostic impact.…”

Section: Myc and Bcl2 Overexpressionmentioning

confidence: 99%

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Double hit and double expressors in lymphoma: Definition and treatment

Riedell

Smith

2018

Cancer

148

118

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Emerging biologic subsets and new prognostic markers are significantly and adversely affecting curability after standard chemoimmunotherapy for aggressive B-cell lymphomas. The identification of concurrent MYC and B-cell CLL/lymphoma 2 (BCL2) deregulation, whether at a genomic or protein level, has opened a new era of investigation within the most common subtype of aggressive B-cell lymphomas. Double-hit lymphoma (DHL), defined as a dual rearrangement of MYC and BCL2 and/or B-cell CLL/lymphoma 6 (BCL6) genes, is an uncommon subset accounting for 5% to 7% of all diffuse large B-cell lymphomas (DLBCLs), and long-term survivors are rare. Double-expressor lymphoma (DEL), defined as overexpression of MYC and BCL2 proteins not related to underlying chromosomal rearrangements, is not a distinct entity in the current World Health Organization classification but accounts for 20% to 30% of DLBCL cases and also has poor outcomes. There are many practical considerations related to identifying, determining the prognosis of, and managing DHL and DEL. Cancer 2018;124:4622-4632.

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Section: Mycmentioning

confidence: 99%

Section: Mycmentioning

confidence: 99%

Section: Myc and Bcl2 Overexpressionmentioning

confidence: 99%

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Double hit and double expressors in lymphoma: Definition and treatment

Riedell

Smith

2018

Cancer

148

118

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“…52,53 However, this has not been consistently shown to be associated with increased MYC protein expression or an inferior clinical outcome. 17,[53][54][55][56][57][58] Other factors can affect MYC levels without directly altering the integrity or location of the MYC locus. Many signaling pathways, including BCR and NF-kB signaling, can lead to increased transcription of MYC through direct and indirect interactions at the MYC promoter as reviewed by Wierstra and Alves.…”

Section: 44mentioning

confidence: 99%

Approach to the diagnosis and treatment of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements

Sesques

Johnson

2017

Blood

138

116

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High-grade B-cell lymphomas (HGBLs) with MYC and BCL2 and/or BCL6 rearrangements, so-called “double-hit” lymphomas (HGBL-DH), are aggressive lymphomas that form a separate provisional entity in the 2016 revised World Health Organization Classification of Lymphoid Tumors. Fluorescence in situ hybridization (FISH) will be required to identify HGBL-DH and will reclassify a subset of diffuse large B-cell lymphomas (DLBCLs) and HGBLs with features intermediate between DLBCL and Burkitt lymphoma into this new category. Identifying patients with HGBL-DH is important because it may change clinical management. This poses a challenge for centers that may not be ready to handle the additional workload and financial burden associated with the increase in requests for FISH testing. Herein, we review the mechanisms of deregulation of these oncogenes. We identify the factors associated with a poor prognosis and those that can guide diagnostic testing. Restricting FISH analysis to the 10% of DLBCL patients who have a germinal center B-cell phenotype and coexpress MYC and BCL2 proteins would be cost-effective and would identify the subset of patients who are at highest risk of experiencing a relapse following conventional therapy. These patients may benefit from intensified chemotherapy regimens or, ideally, should enroll in clinical trials investigating novel regimens.

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“…Among the published immunohistochemical algorithms, the Hans algorithm was most widely used in routine practice and prognostic significance has been questioned, especially in the chemoimmunotherapy era [15][16][17][18][19] . As described before, this case with MYC, BCL 2 and BCL 6 translocations was classified as a triple hit lymphoma (THL), which has the worst outcome 20,21 . The clinical implications of a correct diagnosis of this entity are significant because of the fact that triple hit lymphomas have shown worse clinical prognosis than either DLBCL or Burkitt lymphoma (BL).…”

Section: Discussionmentioning

confidence: 99%

Case report. A rare case of triple-hit diffuse large B-cell lymphoma of the parotid gland in a patient with Sjogren’s syndrome

Birceanu

Evsei

Dumitru

et al. 2017

Romanian Journal of Rhinology

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A rare case of triple-hit diffuse large B-cell lymphoma of the parotid gland in a patient with Sjogren's syndrome CASE REPORT INTRODUCTIONPrimary lymphoma of the salivary gland is rare, accounting for 2-5% of all salivary neoplasms. Diffuse large B-cell lymphomas (DLBCL) are uncommon, most salivary gland lymphoid malignancies being lowgrade lymphomas with MALT (mucosa associated lymphoid tissue) lymphomas being the most common. The majority of primary salivary gland DLBCLs appear to arise from MALT type lymphomas in a background of sialadenitis associated with autoimmune disorders, such as Sjogren syndrome [1][2][3][4] . The pathophysiology of Non-Hodgkin Lymphoma (NHL) is unknown. However, some risk factors are related to NHL development, such as acquired or druginduced immunodeficiency, some autoimmune diseases or Sjogren's syndrome 5 . Double and triple-hit B-cell lymphoma (DHL, THL) are rare lymphoma subtypes usually associated with poor prognosis. These specific subtypes are defined by two or three recurrent chromosome translocations: MYC/8q24loci, usually in combination with the t(14;18)(q32; q21) bcl-2 gene and/or BCL6 3q27 chromosomal translocation. Here, we present one case with diffuse large B-cell lymphoma associated with follicular lymphoma transformed to THL 6 . ABSTRACT BACKGROUND. Primary malignant lymphomas of the salivary gland are rare, accounting for 2% of salivary gland tumors and 5% of all extranodal lymphomas. The clinical presentation is not particularly characteristic, a feature that usually leads to diagnostic and treatment delays. CASE REPORT.We report a case of a parotid gland triple-hit diffuse large B-cell (DLBCL) lymphoma associated with follicular lymphoma in a 76-year-old female patient with a unique personal history, which included a diagnosis of Sjogren Syndrome and exposure to a toxic working environment with pesticides. Diffuse large B-cell lymphomas are uncommon given the fact that most lymphoid malignancies are low-grade lymphomas, with MALT (mucosa associated lymphoid tissue) lymphomas being the most common. Triple-hit DLBCL are extremely rare and the diagnosis can be challenging. Parotidectomy, as the first step, must be followed by histopathology and immunohistochemistry for final diagnosis and treatment.CONCLUSION. This case highlights the fact that B-cell lymphoma in the salivary gland can be unrecognized due to unspecific symptoms and requires immunohistochemistry studies for confirmation. It is important to recognize triple-hit lymphoma due to its worse prognosis and differentiated treatment. Patients with Sjogren syndrome have additional risk factors for progression to lymphoma.

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MYC or BCL2 copy number aberration is a strong predictor of outcome in patients with diffuse large B-cell lymphoma

Cited by 49 publications

References 35 publications

Double hit and double expressors in lymphoma: Definition and treatment

Double hit and double expressors in lymphoma: Definition and treatment

Approach to the diagnosis and treatment of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements

Case report. A rare case of triple-hit diffuse large B-cell lymphoma of the parotid gland in a patient with Sjogren’s syndrome

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