Hyperactivated STAT3 in ALK–positive diffuse large B-cell lymphoma with clathrin-ALK fusion

Momose, Shuji; Tamaru, Jun‐ichi; Kishi, Hirohisa; Mikata, Ittaku; Mori, Masaya; Toyozumi, Yasuo; Itoyama, Shinji

doi:10.1016/j.humpath.2008.06.009

Cited by 36 publications

(27 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…STAT3 is a downstream effector of ALK and is phosphorylated in ALK-positive LBCL. 73,91,92 STAT3 also induces the expression of BLIMP1, promoting plasma cell differentiation ( Figure 2B). Similar to PBL, the activation of MYC by STAT3 may be a mechanism to overcome the repressing effects of BLIMP1.…”

Section: Dh/th Lymphomamentioning

confidence: 94%

Understanding MYC-driven aggressive B-cell lymphomas: pathogenesis and classification

Ott

Rosenwald

Campo

2013

Blood

223

214

View full text Add to dashboard Cite

MYC is a potent oncogene initially identified as the target of the t(8;14)(q24;q32) chromosome translocation in Burkitt lymphoma. MYC gene alterations have been identified in other mature B-cell neoplasms that are usually associated with an aggressive clinical behavior. Most of these tumors originate in cells that do not normally express MYC protein. The oncogenic events leading to MYC up-regulation seem to overcome the inhibitory effect of physiological repressors such as BCL6 or BLIMP1.Aggressive lymphomas frequently carry additional oncogenic alterations that cooperate with MYC dysregulation, likely counteracting its proapoptotic function. The development of FISH probes and new reliable antibodies have facilitated the study of MYC gene alterations and protein expression in large series of patients, providing new clinical and biological perspectives regarding MYC dysregulation in aggressive lymphomas. MYC gene alterations in large B-cell lymphomas are frequently associated with BCL2 or BCL6 translocations conferring a very aggressive behavior. Conversely, MYC protein up-regulation may occur in tumors without apparent gene alterations, and its association with BCL2 overexpression also confers a poor prognosis. In this review, we integrate all of this new information and discuss perspectives, challenges, and open questions for the diagnosis and management of patients with MYC-driven aggressive B-cell lymphomas. (Blood. 2013;122(24):3884-3891) Introduction MYC was initially identified as the target oncogene dysregulated by the t(8;14)(q24;q32) translocation in Burkitt lymphoma (BL). MYC rearrangements involving the heavy-and light-chain immunoglobulin (IGL) loci and different non-IG genes were subsequently detected in other lymphoid neoplasms usually associated with very aggressive clinical behavior.1,2 The transforming oncogenic potential of MYC was initially demonstrated in cell lines and transgenic animal models. However, MYC dysregulation alone does not cause lymphoma, 4 and the t(8;14) has been found at very low levels in blood and BM of healthy individuals, 5 indicating that this genetic alteration per se is not sufficient to trigger lymphomagenesis. BL and most lymphomas carrying MYC translocations are among the most proliferative tumors. However, MYC expression has been difficult to identify in the germinal center (GC), the lymphoid cell compartment with the highest proliferative fraction, where most of these tumors originate. Understanding the possible role of MYC in normal lymphoid regulation and particularly the modulation of the GC reaction has been elusive.Recent studies, including basic immunology analyses, new animal models, next-generation sequencing, and clinicopathological observations, are converging to provide a new perspective of the role of MYC in the lymphoid system and the pathogenesis of aggressive lymphomas. In this review, we integrate all of this new information and discuss new perspectives, challenges, and open questions for the diagnosis and management of patients. MYC as a transc...

show abstract

Section: Dh/th Lymphomamentioning

confidence: 94%

Understanding MYC-driven aggressive B-cell lymphomas: pathogenesis and classification

Ott

Rosenwald

Campo

2013

Blood

223

214

View full text Add to dashboard Cite

show abstract

“…Histologically, they display monomorphic, large immunoblastic/plasmablastic cells, which are CD138-, EMA-, CD4-, and cytoplasmic IgA-positive but lack CD30 and B-cellrestricted markers , Reichard et al 2007). ALK C DLBCL are characterized by an aggressive outcome and poor response to treatment (Reichard et al 2007, Stachurski et al 2007, Choung et al 2008, Momose et al 2009). …”

Section: Alk Fusion Proteinsmentioning

confidence: 99%

Anaplastic lymphoma kinase in human cancer

Barreca

Lasorsa

Riera

et al. 2011

Journal of Molecular Endocrinology

122

View full text Add to dashboard Cite

The receptor tyrosine kinases (RTKs) play a critical role, controlling cell proliferation, survival, and differentiation of normal cells. Their pivotal function has been firmly established in the pathogenesis of many cancers as well. The anaplastic lymphoma kinase (ALK), a transmembrane RTK, originally identified in the nucleophosmin (NPM)-ALK chimera of anaplastic large cell lymphoma, has emerged as a novel tumorigenic player in several human cancers. In this review, we describe the expression of the ALK-RTK, its related fusion proteins, and their molecular mechanisms of activation. Novel tailored strategies are briefly illustrated for the treatment of ALK-positive neoplasms.

show abstract

“…The t(2;5)(p23;q35) and/or NPM1-ALK fusion, flagged by a nuclear and cytoplasmic ALK immunostaining, was reported in 10% of ALK + LBCL cases. [3][4][7][8][9][10] It is noteworthy that ALK-involving translocations were originally identified in ALK + T-/null-cell anaplastic large cell lymphoma. 11 Interestingly, the same aberrations have been detected in inflammatory myofibroblastic tumors (IMT) 12 and non-small cell lung cancer.…”

Section: Introductionmentioning

confidence: 99%

ALK-positive large B-cell lymphomas with cryptic SEC31A-ALK and NPM1-ALK fusions

et al. 2010

View full text Add to dashboard Cite

Hyperactivated STAT3 in ALK–positive diffuse large B-cell lymphoma with clathrin-ALK fusion

Cited by 36 publications

References 26 publications

Understanding MYC-driven aggressive B-cell lymphomas: pathogenesis and classification

Understanding MYC-driven aggressive B-cell lymphomas: pathogenesis and classification

Anaplastic lymphoma kinase in human cancer

ALK-positive large B-cell lymphomas with cryptic SEC31A-ALK and NPM1-ALK fusions

Contact Info

Product

Resources

About