Molecular profiling reveals immunogenic cues in anaplastic large cell lymphomas with DUSP22 rearrangements

Luchtel, Rebecca A.; Dasari, Surendra; Oishi, Naoki; Pedersen, Martin Bjerregård; Hu, Guojie; Rech, Karen L.; Ketterling, Rhett P.; Sidhu, Jagmohan S.; Wang, Xueju; Katoh, Ryohei; Doğan, Ahmet; Kip, N. Sertac; Cunningham, Julie M.; Sun, Zhifu; Baheti, Saurabh; Porcher, Julie C.; Said, Jonathan; Jiang, Liuyan; Hamilton-Dutoit, Stephen; Møller, Michael; Nørgaard, Peter; Bennani, N. Nora; Chng, Wee Joo; Huang, Gaofeng; Link, Brian K.; Facchetti, Fabio; Cerhan, James R.; d’Amore, Francesco; Ansell, Stephen M.; Feldman, Andrew L.

doi:10.1182/blood-2018-03-838524

Cited by 100 publications

(110 citation statements)

References 70 publications

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“…DUSP22—IRF4 rearrangements t(6:7) confer a good prognosis with 5‐year survival rates approaching 90% whereas TP63 overexpression from mutations or chromosomal changes results in a poor prognosis with a reported 5‐year survival of 17% . Interestingly, DUSP22 rearrangements are associated with lack of activated STAT3, consistent with this group having a good prognosis . Similarly TP53 and PRDM1 losses are more common in ALK− ALCL and may be associated with a more aggressive clinical course.…”

Section: Molecular Pathogenesis Of Ptcl Subtypesmentioning

confidence: 87%

Aggressive T‐cell lymphomas: 2019 updates on diagnosis, risk stratification, and management

Zain

2019

American J Hematol

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Introduction Aggressive T‐cell lymphomas continue to have a poor prognosis. There are over 27 different subtypes of peripheral T‐cell lymphoma (PTCL) and we are now beginning to understand the differences between the various subtypes beyond histologic variations. Molecular pathogenesis of various subtypes of PTCL Gene expression profiling can help in diagnosis and prognostication of various subtypes including PTCL‐nos and anaplastic large cell lymphoma. In addition, mutational analysis is now being incorporated in clinical trials of novel agents to evaluate various biomarkers of response to allow better therapeutic choices for patients. Targeted therapies There are many targeted agents currently in various stages of clinical trials for PTCL that take advantage of the differential expression of specific proteins or receptors in PTCL tumors. The most promising is the CD30 directed antibody drug conjugate brentuximab vedotin. This has recently been approved by the Food and Drug Administration for the upfront treatment of CD30 expressing PTCLs in combination with cyclophosphamide, doxorubicin, and prednisone chemotherapy. Other notable targets are CD25, CCR4 tag, PI3kinase inhibitors, and JAK/STAT inhibitors. Anaplastic lymphoma kinase (ALK) inhibitors are promising for ALK expressing tumors. Immunotherapies The use of checkpoint inhibitors in the treatment of PTCL is still controversial. The most promising results have been seen in cases of extranodal natural killer cell/T‐cell lymphomas and cutaneous T‐cell lymphomas. For all other subtypes, immune checkpoint inhibitors should be used with extreme caution and only in the context of a clinical trial. Allogeneic stem cell transplant continues to be the curative therapy for most aggressive subtypes of PTCL.

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Section: Molecular Pathogenesis Of Ptcl Subtypesmentioning

confidence: 87%

Aggressive T‐cell lymphomas: 2019 updates on diagnosis, risk stratification, and management

Zain

2019

American J Hematol

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“…7). 70 Compared to other ALCLs, these cases have unique molecular features-lack of STAT3 activation, DNA hypomethylation and an immunogenic phenotype (expression of cancer-testis antigens, reduced expression of PD-L1, high expression of CD58 and HLA class II) 75 -and frequently harbour a hotspot MSC E116K mutation in the musculin gene. 76 TP63 rearrangements encoding fusion proteins homologous to a dominant-negative p63 isoform define another genetic subgroup of ALK− ALCL (8% of the cases).…”

Section: Anaplastic Large Cell Lymphomas Alk-negative (Alk-alcl)mentioning

confidence: 99%

“…70 In addition, a subgroup of ALK-ALCLs have STAT3 activation resulting from rearrangements of other tyrosine kinase genes (TYK2, ROS1, FRK) and/or activating mutations of JAK and/or STAT3. 75 Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) PTCL-NOS is a heterogeneous category including 'by default' all mature T-cell neoplasms that lack the criteria to be categorised within any of the specifically defined PTCL entities. In particular, an important notion introduced in the current WHO classification is the exclusion of nodal PTCLs with a TFH phenotype, defined by the expression of at least two TFH markers.…”

Section: Anaplastic Large Cell Lymphomas Alk-negative (Alk-alcl)mentioning

confidence: 99%

Approach to nodal-based T-cell lymphomas

Leval

2020

Pathology

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Peripheral T-cell lymphomas (PTCLs) represent a heterogeneous group of uncommon malignancies derived from mature T cells and usually characterised by an aggressive clinical course. Their clinical presentation, localisation and pattern of dissemination are highly variable, but the majority of cases present as nodal diseases. The recently revised classification of lymphomas has incorporated many new molecular genetic data derived from gene expression profiling and next generation sequencing studies, which refine the definition and diagnostic criteria of several entities. Nevertheless, the distinction of PTCL from various reactive conditions, and the diagnosis of PTCL subtypes remains notably challenging. Here, an updated summary of the clinicopathological and molecular features of the most common nodal-based PTCLs (angioimmunoblastic T-cell lymphoma and other nodal lymphomas derived from follicular T helper cells, anaplastic large cell lymphomas and peripheral T-cell lymphoma, not otherwise specified) is presented. Practical recommendations in the diagnostic approach to nodal T-cell lymphoproliferations are presented, including indications for the appropriate use and interpretation of ancillary studies. Finally, we discuss commonly encountered diagnostic problems, including pitfalls and mimics in the differential diagnosis with various reactive conditions, and the criteria that allow proper identification of distinct PTCL entities.

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“…CD2 and CD3 expression was frequent and all cases were EMA negative (Table SIII) (Parrilla Castellar et al , ). Most cases were cytotoxic marker‐negative and all were negative for pSTAT3 and PDL1 (Luchtel et al , ) (Table SIII). Taken together, this data suggests that there may be further genetic and/or biological heterogeneity that impacts prognosis, which can only be captured in larger datasets.…”

Section: Baseline Clinical Features Of 91 Patients With Systemic Anapmentioning

confidence: 99%

Identification of high‐risk DUSP22‐rearranged ALK‐negative anaplastic large cell lymphoma

et al. 2019

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Molecular profiling reveals immunogenic cues in anaplastic large cell lymphomas with DUSP22 rearrangements

Abstract: Key Points DUSP22-rearranged ALCLs belong to a distinct subset of ALCLs lacking activated STAT3. DUSP22-rearranged ALCLs have a unique molecular signature characterized by DNA hypomethylation and an immunogenic phenotype.

Cited by 100 publications

References 70 publications

Aggressive T‐cell lymphomas: 2019 updates on diagnosis, risk stratification, and management

Aggressive T‐cell lymphomas: 2019 updates on diagnosis, risk stratification, and management

Approach to nodal-based T-cell lymphomas

Identification of high‐risk DUSP22‐rearranged ALK‐negative anaplastic large cell lymphoma

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