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- Siegele, Bradford J., et al.
(författare)
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N-terminus DUX4-immunohistochemistry is a reliable methodology for the diagnosis of DUX4-fused B-lymphoblastic leukemia/lymphoma (N-terminus DUX4 IHC for DUX4-fused B-ALL)
- 2022
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Ingår i: Genes Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 61:8, s. 449-458
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Tidskriftsartikel (refereegranskat)abstract
- B-lymphoblastic leukemia/lymphoma (B-ALL) is the most common pediatric malignancy and the most commonly diagnosed adult lymphoblastic leukemia. Recent advances have broadened the spectrum of B-ALL, with DUX4 gene fusions implicated in a subclass occurring in adolescents and young adults and harboring a favorable prognosis. DUX4 fusions have been challenging to identify. We aimed to determine whether expression of the DUX4 oncoprotein, as detected by targeted immunohistochemistry, might serve as a surrogate for molecular detection of DUX4 fusions in B-ALL. A cohort of investigational B-ALLs was generated with enrichment for DUX4 fusions by the inclusion of cases with characteristic demographic features and immunophenotypic properties. B-ALLs with mutually exclusive cytogenetics were collected. Immunohistochemical staining by a monoclonal antibody raised against the N-terminus of the DUX4 protein was performed. N-DUX4 immunohistochemistry demonstrated strong, crisp nuclear staining in blasts of seven investigational cases, six of which had nucleic acid material available for molecular evaluation. Five of these cases demonstrated RNA-seq DUX4-fusion positivity. One N-DUX4 immunohistochemistry positive case lacked a definitive DUX4-fusion by RNA-seq, though demonstrated a gene expression profile characteristic of DUX4-rearranged B-ALLs, a CD2+ immunophenotype, and a lack of staining by C-terminus DUX4 antibody immunohistochemistry. At least 83.3% [5/6] positive predictive value. N-DUX4 immunohistochemistry was negative in blasts of three RNA-seq DUX4-fusion-negative cases (3/3; 100% negative predictive value). B-ALLs with mutually exclusive cytogenetic profiles were all N-DUX4 negative (0/10, specificity 100%). N-DUX4 immunohistochemistry is reliable for the distinction of DUX4-rearranged B-ALLs from other B-ALLs. We recommend its use for subclassification of B-ALLs in adolescents and young adults and in B-ALLs that remain “not otherwise specified.”.
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| 2. |
- Western, Benedikte, et al.
(författare)
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Dropout from exercise trials among cancer survivors—An individual patient data meta-analysis from the POLARIS study
- 2024
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - Chichester, West Sussex : Wiley-Blackwell Publishing Inc.. - 0905-7188 .- 1600-0838. ; 34:2, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The number of randomized controlled trials (RCTs) investigating the effects of exercise among cancer survivors has increased in recent years; however, participants dropping out of the trials are rarely described. The objective of the present study was to assess which combinations of participant and exercise program characteristics were associated with dropout from the exercise arms of RCTs among cancer survivors. Methods: This study used data collected in the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study, an international database of RCTs investigating the effects of exercise among cancer survivors. Thirty-four exercise trials, with a total of 2467 patients without metastatic disease randomized to an exercise arm were included. Harmonized studies included a pre and a posttest, and participants were classified as dropouts when missing all assessments at the post-intervention test. Subgroups were identified with a conditional inference tree. Results: Overall, 9.6% of the participants dropped out. Five subgroups were identified in the conditional inference tree based on four significant associations with dropout. Most dropout was observed for participants with BMI >28.4 kg/m2, performing supervised resistance or unsupervised mixed exercise (19.8% dropout) or had low-medium education and performed aerobic or supervised mixed exercise (13.5%). The lowest dropout was found for participants with BMI >28.4 kg/m2 and high education performing aerobic or supervised mixed exercise (5.1%), and participants with BMI ≤28.4 kg/m2 exercising during (5.2%) or post (9.5%) treatment. Conclusions: There are several systematic differences between cancer survivors completing and dropping out from exercise trials, possibly affecting the external validity of exercise effects. © 2024 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.
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