Dual ALK and MYC Rearrangements Leading to an Aggressive Variant of Anaplastic Large Cell Lymphoma

Liang, Xiayuan; Branchford, Brian R.; Greffe, Brian; McGavran, Loris; Carstens, Billie; Meltesen, Lynne; Albano, Edith A.; Quinones, Ralph; Cook, Bruce A.; Graham, Douglas K.

doi:10.1097/mph.0b013e3182815046

Cited by 22 publications

(19 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Translocations affecting MYC are infrequent in these lymphomas and seem to be associated with an aggressive clinical course. [39][40][41] In contrast, a recent study using array comparative genomic hybridization on primary ALCL samples reported recurrent MYC gains. 42 In addition, other MYC upregulating mechanisms may be used by ALCL.…”

Section: Discussionmentioning

confidence: 98%

Essential role of IRF4 and MYC signaling for survival of anaplastic large cell lymphoma

Weilemann

Grau

Erdmann

et al. 2015

Blood

108

119

View full text Add to dashboard Cite

Key Points• IRF4 regulates MYC expression in ALCL.• ALCL survival depends on IRF4/MYC signaling.Anaplastic large cell lymphoma (ALCL) is a distinct entity of T-cell lymphoma that can be divided into 2 subtypes based on the presence of translocations involving the ALK gene (ALK 1 and ALK 2 ALCL). The interferon regulatory factor 4 (IRF4) is known to be highly expressed in both ALK 1 and ALK 2 ALCLs. However, the role of IRF4 in the pathogenesis of these lymphomas remains unclear. Here we show that ALCLs of both subtypes are addicted to IRF4 signaling, as knockdown of IRF4 by RNA interference was toxic to ALCL cell lines in vitro and in ALCL xenograft mouse models in vivo. Gene expression profiling after IRF4 knockdown demonstrated a significant downregulation of a variety of known MYC target genes. Furthermore, our analyses revealed that MYC is a primary target of IRF4, identifying a novel regulatory mechanism of MYC expression and its target gene network in ALCL. MYC, itself, is essential for ALCL survival, as both knockdown of MYC and pharmacologic inhibition of MYC signaling were toxic to ALCL cell lines. Collectively, our results demonstrate that ALCLs are dependent on IRF4 and MYC signaling and that MYC may represent a promising target for future therapies. (Blood. 2015;125(1):124-132)

show abstract

Section: Discussionmentioning

confidence: 98%

Essential role of IRF4 and MYC signaling for survival of anaplastic large cell lymphoma

Weilemann

Grau

Erdmann

et al. 2015

Blood

108

119

View full text Add to dashboard Cite

show abstract

“…In contrast, development of HLH , ITP, and AIHA after establishing the diagnosis of TCL implies generation of autoimmunity secondary to TCL. [5][6] Herein, we review systematically the autoimmune disorders documented in the peer-reviewed literature in patients with T-cell lymphomas.…”

Section: Autoimmunity and T-cell Lymphomamentioning

confidence: 99%

Autoimmune disorders in patients with T-cell lymphoma: a comprehensive review

Bergh

Alvarez-Argote

Panwala

et al. 2015

Current Medical Research and Opinion

View full text Add to dashboard Cite

Autoimmune disorders can develop prior to, during or after the onset of TCL. The diagnosis of TCL should prompt early recognition of certain autoimmune disorders if clinical suspicion exists. A dysfunctional immune response in these patients may be responsible for the occurrence of autoimmunity. Conversely, autoimmune conditions might create a favorable milieu for T-cell lymphoma pathogenesis. Therefore, their presence should increase the suspicion of TCL in an appropriate clinico-laboratory context. There is need for larger studies to assess further the TCL-autoimmunity relationship as prognosis and management of these patients can be considerably affected.

show abstract

“…Using deep RNA sequencing, our group recently identified a novel TRAF1-ALK fusion in an ALCL patient with cytoplasmic ALK immunoreactivity only [9]. Rearrangements of the MYC gene, frequently detected in high-grade B-cell lymphomas, have been reported in 3 cases of ALK-positive ALCL [10–12]. All 3 patients with dual ALK and MYC rearrangements demonstrated an aggressive clinical course, with systemic and extranodal presentation, early tumor relapse, and bone marrow involvement during the course of the disease.…”

Section: Alk Rearrangementsmentioning

confidence: 99%

Genetics of anaplastic large cell lymphoma

Zeng

Feldman

2015

Leukemia & Lymphoma

View full text Add to dashboard Cite

Anaplastic large cell lymphoma (ALCL) comprises a group of T-cell non-Hodgkin lymphomas unified by common morphologic and immunophenotypic characteristics, but with a spectrum of clinical presentations and behaviors. Early identification of anaplastic lymphoma kinase (ALK) gene rearrangements in some ALCLs led to recognition of ALK as an important diagnostic and prognostic biomarker, and a key driver of ALCL pathobiology. Rearrangements and other genetic abnormalities of ALK subsequently were identified in diverse other human malignancies. Recent clinical, pathologic, and genetic data have begun to shed light on ALK-negative ALCLs, revealing significant heterogeneity within this more ill-defined entity.

show abstract

Dual ALK and MYC Rearrangements Leading to an Aggressive Variant of Anaplastic Large Cell Lymphoma

Cited by 22 publications

References 18 publications

Essential role of IRF4 and MYC signaling for survival of anaplastic large cell lymphoma

Essential role of IRF4 and MYC signaling for survival of anaplastic large cell lymphoma

Autoimmune disorders in patients with T-cell lymphoma: a comprehensive review

Genetics of anaplastic large cell lymphoma

Contact Info

Product

Resources

About