Comprehensive serum cytokine analysis identifies IL-1RA and soluble IL-2Rα as predictors of event-free survival in T-cell lymphoma

Gupta, Mamta; Stenson, Mary; O’Byrne, Megan M.; Maurer, Matthew J.; Habermann, Thomas M.; Cerhan, James R.; Weiner, George J.; Witzig, Thomas E.

doi:10.1093/annonc/mdv486

Cited by 33 publications

(27 citation statements)

References 33 publications

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“…by guest www.bloodjournal.org From circulating epidermal growth factor levels, and enrichment for somatic mutations targeting the ERBB signaling pathway. 47,78,79 We also rediscovered a previously reported ATXN1-TP63 fusion. TP63 rearrangements are recurrent in PTCL, NOS and ALK-negative ALCL and are characterized by high proliferation indices and poor prognosis.…”

Section: Discussionmentioning

confidence: 80%

Integrated mate-pair and RNA sequencing identifies novel, targetable gene fusions in peripheral T-cell lymphoma

Boddicker¹,

Razidlo

Dasari

et al. 2016

Blood

100

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Peripheral T-cell lymphomas (PTCLs) represent a heterogeneous group of T-cell malignancies that generally demonstrate aggressive clinical behavior, often are refractory to standard therapy, and remain significantly understudied. The most common World Health Organization subtype is PTCL, not otherwise specified (NOS), essentially a “wastebasket” category because of inadequate understanding to assign cases to a more specific diagnostic entity. Identification of novel fusion genes has contributed significantly to improving the classification, biologic understanding, and therapeutic targeting of PTCLs. Here, we integrated mate-pair DNA and RNA next-generation sequencing to identify chromosomal rearrangements encoding expressed fusion transcripts in PTCL, NOS. Two of 11 cases had novel fusions involving VAV1, encoding a truncated form of the VAV1 guanine nucleotide exchange factor important in T-cell receptor signaling. Fluorescence in situ hybridization studies identified VAV1 rearrangements in 10 of 148 PTCLs (7%). These were observed exclusively in PTCL, NOS (11%) and anaplastic large cell lymphoma (11%). In vitro, ectopic expression of a VAV1 fusion promoted cell growth and migration in a RAC1-dependent manner. This growth was inhibited by azathioprine, a clinically available RAC1 inhibitor. We also identified novel kinase gene fusions, ITK-FER and IKZF2-ERBB4, as candidate therapeutic targets that show similarities to known recurrent oncogenic ITK-SYK fusions and ERBB4 transcript variants in PTCLs, respectively. Additional novel and potentially clinically relevant fusions also were discovered. Together, these findings identify VAV1 fusions as recurrent and targetable events in PTCLs and highlight the potential for clinical sequencing to guide individualized therapy approaches for this group of aggressive malignancies.

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Section: Discussionmentioning

confidence: 80%

Integrated mate-pair and RNA sequencing identifies novel, targetable gene fusions in peripheral T-cell lymphoma

Boddicker¹,

Razidlo

Dasari

et al. 2016

Blood

100

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“…The prognostic significance of pre‐treatment ALC/AMC ratios and serum cytokine concentrations has been described in both NHL and HL, however, the relationship between these prognostic factors and the underlying mechanisms remain largely unknown. We hypothesized that patients with elevated serum cytokines, either being produced by the tumor cells or originating in the tumor microenvironment, would be more likely to have suppressed ALC/AMC ratios.…”

Section: Discussionmentioning

confidence: 99%

“…In follicular lymphoma (FL) elevated IL‐2R, IL‐1Rα, and MIG concentrations were associated with inferior EFS . In T‐cell lymphoma (TCL) elevated IL‐1Rα and IL‐2R concentrations were associated with inferior EFS …”

Section: Introductionmentioning

confidence: 99%

Associations between elevated pre‐treatment serum cytokines and peripheral blood cellular markers of immunosuppression in patients with lymphoma

et al. 2017

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Higher ratios of the pre-treatment peripheral blood absolute lymphocyte (ALC) to absolute monocyte counts (AMC) are associated with improved outcomes in lymphoma. Conversely, elevated pre-treatment serum cytokines are associated with inferior outcomes. The relationship between pre-treatment serum cytokines and ALC/AMC ratios remains unknown. We studied twelve serum cytokines and the ALC/AMC ratios in 390 patients with untreated diffuse large B-cell, follicular, mantle cell, T-cell, and Hodgkin lymphoma. Different pre-treatment serum cytokine concentrations correlated with ALC, AMC, and ALC/AMC ratios depending on the lymphoma type. In the entire cohort (n = 390) lower ALC/AMC ratios modestly correlated with higher IL-2R (r = -0.36), IL-12 (r = -0.17), IP-10 (r = -0.23), and MIG (r = -0.32) concentrations (p < 0.001). Elevated IL-2R was independently associated with suppressed ALC (OR 2.69, 95% CI 1.77-4.07, p < 0.001), elevated AMC (OR 2.05, 95% CI 1.34-3.14, p < 0.001), and suppressed ALC/AMC ratios (OR 3.51, 95% CI 2.31-5.34, p < 0.001). Both elevated IL-2R (HR 2.27, 95% CI 1.48-3.49, p < 0.001) and suppressed ALC/AMC ratios (HR 1.53, 95% CI 1.03-2.28, p = 0.037) were independently associated with inferior overall survival. These data support the notion that elevated serum cytokines are immunosuppressive and provide further rationale to target the tumor microenvironment for therapeutic benefit.

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“…A pelvic examination including visual inspection, bimanual and ultrasonographic evaluation was performed to all patients. In addition to a cervical smear obtained with a cytobrush (ecto and endocervical), HPV DNA testing was conducted on specimen transport medium (STM) samples using the Hybrid Capture tube test (Digene Corp.) formatted to detect 13 HPV types (16,18,31,33,35,39,45, 51, 52, 56, 58, 59 and 68) [19]. Pap smears were classified according to the 2001 Bethesda system of reporting for cervical cytology [20].…”

Section: Methodsmentioning

confidence: 99%

“…Levels of sIL-2R can be measured easily because a part of it is proteolytically cleaved and is found in serum [10]. Previous studies have demonstrated elevated serum levels of sIL-2R in various autoimmune disorders such as rheumatoid arthritis, systemic lupus erythematosus or Kawasaki disease, among transplant recipients who subsequently reject their graft, and in individuals with viral infections, including HIV and hepatitis, or hematological and lung tumors, as well as precancer and cancer of the uterine cervix [11][12][13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Serum levels of soluble interleukin-2 receptor in association with oxidative stress index in patients with different types of HPV

et al. 2017

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Objectives: The aim of this paper is to determine the oxidative-antioxidative status and levels of soluble interleukin-2 receptor (sIL-2R) in serum of patients with different types of HPV infections and to compare it with patients who are negative for HPV. Material and methods:A total of 80 women were divided into three groups as follows: Group 1 consisted of 25 women who were positive for HPV types 16 or 18; Group 2 consisted of 25 women who were positive for other types of HPV including type 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 or 68; Group 3 consisted of 30 patients who were negative for HPV as a control group. Serum sIL-2R and plasma oxidative stress index (OSI) were analyzed.Results: Serum sIL-2R levels were significantly higher in group 1 compared to group 2 and 3. OSI was found significantly increased in groups 1 and 2 compared to group 3. Also, we found a weak positive correlation between IL-2R and OSI.Conclusion: sIL-2R and oxidative stress may have a role in HPV infection, especially in case of high-risk types.

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Comprehensive serum cytokine analysis identifies IL-1RA and soluble IL-2Rα as predictors of event-free survival in T-cell lymphoma

Cited by 33 publications

References 33 publications

Integrated mate-pair and RNA sequencing identifies novel, targetable gene fusions in peripheral T-cell lymphoma

Integrated mate-pair and RNA sequencing identifies novel, targetable gene fusions in peripheral T-cell lymphoma

Associations between elevated pre‐treatment serum cytokines and peripheral blood cellular markers of immunosuppression in patients with lymphoma

Serum levels of soluble interleukin-2 receptor in association with oxidative stress index in patients with different types of HPV

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