SOX11 is a biomarker for cyclin D1-negative mantle cell lymphoma

Narurkar, Roshni; Alkayem, Mohammad; Liu, Delong

doi:10.1186/s40364-016-0060-9

Cited by 30 publications

(15 citation statements)

References 20 publications

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“…However, since the first report of specific nuclear expression of SOX11 in MCL in 2008 [11], there has been much research interest in this transcription factor. It has been accepted generally that nuclear SOX11 is not only highly expressed in conventional MCL cells, but also in CCND1cases [14]. SOX11 has also been suggested to be a prognostic marker in MCL, but data on this are quite conflicting.…”

Section: Discussionmentioning

confidence: 99%

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miR-223 is repressed and correlates with inferior clinical features in mantle cell lymphoma through targeting SOX11

Zhou

Feng

Wang

et al. 2018

Experimental Hematology

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Mantle cell lymphoma (MCL) is an aggressive lymphoid malignancy characterized by cytogenetic aberration of t(11;14), although it is not the prerequisite. Until now, the pathogenesis of MCL has not been fully interpreted. Our current study showed that microRNA (miR)-223 was downregulated in purified CD19 lymphocytes from MCL patients (n = 21) compared with that of healthy donors (n = 20). In addition, patients with a high-risk Mantle Cell Lymphoma International Prognostic Index (MIPI) score, elevated lactate dehydrogenase, and Eastern Cooperative Oncology Group performance status >2 were more likely to have much lower miR-223 expression. Furthermore, low miR-223 expression predicted inferior overall survival regardless of treatment in our cohort of 21. To explore the role of miR-223 in MCL, we constructed an ectopic miR-223 MCL cell line and revealed that miR-223 inhibited cell proliferation and promoted G/G accumulation and cell apoptosis. A database search showed that SOX11, a crucial transcription factor in MCL, is the putative target of miR-223. In support of this, we observed a much lower level of SOX11 protein in miR-223-overexpressing cells than in parental cells. Further, the luciferase reporter assay confirmed that miR-223 at the posttranscriptional level suppressed the wild-type 3'-untranslated region of SOX11 but not the mutated one. Finally, miR-223 was found to be negatively correlated with the mRNA level of SOX11 in clinical samples. Our work demonstrates for the first time that miR-223 is repressed and correlated with high-risk clinical features in MCL, which provides a potential molecule to target to optimize MCL management.

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Section: Discussionmentioning

confidence: 99%

“…SOX11 belongs to a group of 20 transcription factors within the high-mobility group box protein superfamily [10], is expressed at higher levels in MCL patients, and is specific for MCL, unlike other NHLs [11][12][13]. Further, the presence of SOX11 is also a useful identifier of CCND1 -MCL [14]. However, studies on the regulation of SOX11 in MCL are scarce.…”

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confidence: 99%

miR-223 is repressed and correlates with inferior clinical features in mantle cell lymphoma through targeting SOX11

Zhou

Feng

Wang

et al. 2018

Experimental Hematology

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“…It is to be noted that cyclin D1 (CCND1) protein overexpression and/or the t(11;14)(q13;q32) translocation are the pathognomonic hallmarks of MCL. Nevertheless, SOX11 expression can be used as a biomarker for most cases of MCL that lacked both t(11;14) and cyclin D1 protein but still had a gene expression profile suggesting a diagnosis of MCL [ 6 ]. Another subtype of MCL develops from IGHV-hypermutated, SOX11 negative B cells.…”

Section: Introductionmentioning

confidence: 99%

Current trials for frontline therapy of mantle cell lymphoma

2018

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Mantle cell lymphoma (MCL) is a rare and incurable subtype of non-Hodgkin’s lymphoma that generally affects older individuals. However, the use of high-dose therapy and autologous stem cell transplant has improved significantly the prognosis of this hematological malignancy, but at the cost of increased toxicities, such as acute toxic death and secondary malignancies. But thanks to a rising understanding of the biology of MCL, the explosion of specifically targeted new efficacious agents, immunotherapy agents, and cellular therapies in the frontline setting, the prognosis of MCL is expected to improve dramatically.The initial treatment of MCL is currently not standardized and the therapeutic landscape of MCL is rapidly evolving. This review provides an extensive overview of the current frontline therapy trials for MCL and presents the results of innovative regimen, including some integrating novel agents and desintensified chemotherapy.

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“…Mantle cell lymphoma (MCL) accounts for 3 to 6% of non-Hodgkin lymphomas and is generally characterized by cyclin D1 overexpression and, more recently, by SOX11 expression [ 1 – 3 ]. MCL is generally considered incurable with standard chemoimmunotherapy and approved targeted agents [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Observational study of lenalidomide in patients with mantle cell lymphoma who relapsed/progressed after or were refractory/intolerant to ibrutinib (MCL-004)

et al. 2017

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BackgroundThe observational MCL-004 study evaluated outcomes in patients with relapsed/refractory mantle cell lymphoma who received lenalidomide-based therapy after ibrutinib failure or intolerance.MethodsThe primary endpoint was investigator-assessed overall response rate based on the 2007 International Working Group criteria.ResultsOf 58 enrolled patients (median age, 71 years; range, 50–89), 13 received lenalidomide monotherapy, 11 lenalidomide plus rituximab, and 34 lenalidomide plus other treatment. Most patients (88%) had received ≥ 3 prior therapies (median 4; range, 1–13). Median time from last dose of ibrutinib to the start of lenalidomide was 1.3 weeks (range, 0.1–21.7); 45% of patients had partial responses or better to prior ibrutinib. Primary reasons for ibrutinib discontinuation were lack of efficacy (88%) and ibrutinib toxicity (9%). After a median of two cycles (range, 0–11) of lenalidomide-based treatment, 17 patients responded (8 complete responses, 9 partial responses), for a 29% overall response rate (95% confidence interval, 18–43%) and a median duration of response of 20 weeks (95% confidence interval, 2.9 to not available). Overall response rate to lenalidomide-based therapy was similar for patients with relapsed/progressive disease after previous response to ibrutinib (i.e., ≥PR) versus ibrutinib-refractory (i.e., ≤SD) patients (30 versus 32%, respectively). The most common all-grade treatment-emergent adverse events after lenalidomide-containing therapy (n = 58) were fatigue (38%) and cough, dizziness, dyspnea, nausea, and peripheral edema (19% each). At data cutoff, 28 patients have died, primarily due to mantle cell lymphoma.ConclusionLenalidomide-based treatment showed clinical activity, with no unexpected toxicities, in patients with relapsed/refractory mantle cell lymphoma who previously failed ibrutinib therapy.Trial registration Clinicaltrials.gov identifier NCT02341781. Date of registration: January 14, 2015Electronic supplementary materialThe online version of this article (10.1186/s13045-017-0537-5) contains supplementary material, which is available to authorized users.

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SOX11 is a biomarker for cyclin D1-negative mantle cell lymphoma

Cited by 30 publications

References 20 publications

miR-223 is repressed and correlates with inferior clinical features in mantle cell lymphoma through targeting SOX11

miR-223 is repressed and correlates with inferior clinical features in mantle cell lymphoma through targeting SOX11

Current trials for frontline therapy of mantle cell lymphoma

Observational study of lenalidomide in patients with mantle cell lymphoma who relapsed/progressed after or were refractory/intolerant to ibrutinib (MCL-004)

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