Mannan-binding lectin (MBL) and MBL-associated serine protease-2 (MASP-2) are two key components of the lectin-pathway of complement-activation. Information on the potential role of lectin-pathway ...components in carcinogenesis versus immune surveillance of cancer is scarce. This study aimed to determine if serum concentrations of MBL and MASP-2 differ between children with cancer and healthy age-matched controls.
In this retrospective multicentre study, MBL and MASP-2 were measured by commercially available ELISA in frozen remnants of serum taken at diagnosis in paediatric patients with cancer. For six diagnostic groups, these concentrations were compared with serum concentrations of age-matched healthy controls using exact Wilcoxon signed-rank tests.
MBL and MASP-2 were measured in serum of 372 patients. MBL was significantly higher in patients with solid tumours vs. controls (median, 2,799 vs. 1,917 μg/L; P = 0.008), and MASP-2 was significantly higher in patients with acute lymphoblastic leukaemia (406 vs. 317 μg/L; P = 0.009), Non-Hodgkin lymphoma (361 vs. 293 μg/L; P = 0.037) and CNS tumors (463 vs. 296 μg/L; P = 0.002).
These results may indicate a role of MBL and MASP-2 in the initiation or progression of specific paediatric cancers, while other mechanisms remain possible as well. Larger, disease-specific studies are warranted for confirmation and for elucidation of the underlying mechanisms.
Several studies have demonstrated that patients with childhood acute lymphoblastic leukemia presenting with mild anemia at diagnosis have an increased risk of poor outcome compared to patients with ...more severe anemia. However, it has not been reported whether there is any correlation between degree of anemia and leukemia subtype.
In a cohort of 1162 patients with childhood acute lymphoblastic leukemia we analyzed whether there was a correlation between degree of anemia and leukemia subtype. We also studied the association between degree of anemia and event-free survival within the subtypes.
Hemoglobin levels at diagnosis were distributed in a non-random pattern. The degree of anemia was significantly different for three distinct groups of patients compared to the remaining patients (mean hemoglobin; T-cell leukemia: 106 g/L versus 76 g/L (precursor B-cell acute lymphoblastic leukemia); within precursor B-cell ALL: TEL-AML1 positive: 68 g/L versus 79 g/L; BCR-ABL positive: 93 g/L versus 76 g/L; each p<0.05). Furthermore, in contrast to the entire study group, patients with T-cell leukemia, TEL-AML1(+), and BCR-ABL(+) precursor B-cell leukemia had a more favorable prognosis if presenting with a higher hemoglobin level (>/=80 g/L).
These observations indicate that the formerly reported direct correlation between severity of anemia and survival in childhood acute lymphoblastic leukemia mainly reflects differences in the degree of anemia between distinct biological subgroups with different treatment outcomes. On the other hand, the inverse relationship between severity of anemia and survival found within specific subgroups suggests that very low hemoglobin levels at diagnosis are associated with more advanced disease in these subgroups.
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/locate/withdrawalpolicy).
This article is being retracted due to the retraction of the ...article for which it served as a correction.
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/locate/withdrawalpolicy).
This article is being retracted at the request of the Editor.
...Concern has been raised about authorship irregularities on this paper. One of the authors on the paper contacted the Journal to allege that the paper submitted to Neoplasia had been published without their permission, despite having been involved in earlier versions of the work. Despite an investigation, no evidence could be provided that proved all authors had agreed to the submission of this manuscript to Neoplasia. In addition, a co-author was added to the paper after submission, without the permission of the Editor and without signed agreement from all authors. Changing authors after submission without permission from the editor is against the journal policy as is stated in the “Changes to Authorship” section of the Guide for Authors (https://www.elsevier.com/journals/neoplasia/1476-5586/guide-for-authors).
The authors responded to requests for clarification on these points, but those explanations did not satisfactorily address all the concerns. As such and due to the nature of the authorship irregularities uncovered, the Editor has decided to retract the article. The scientific community takes a very strong view on this matter and apologies are offered to readers.
Real-time reverse transcription polymerase chain reaction (RT-PCR) assays were developed for the quantification of expression of the genes for human interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, ...IL-12, IL-15, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β and for the endogenous reference hydroxymethylbilane synthase (HMBS). The assays detected as little as five plasmid copies and were 100% specific. The creation and integration of a calibration sample into the assays permitted their calibration across experiments. To handle the high number of generated data, the correlator of advanced real-time assays (CARTA) software was designed to organize samples and to automatically control and analyze TaqMan™ real-time RT-PCR data. The RT-PCR assays were applied to quantify levels of cytokine gene expression in human palatine tonsils at excision and during 4 days of histoculture. Similar longitudinal patterns of cytokine gene expression were observed in all donors, but the variations in spontaneous expression levels between donors were large. The expression levels in histocultures were constant over time and similar to the expression levels at excision except for IL-6 and IL-8, which markedly increased following the first 24 h of culture, possibly due to the initial stress. The standardized and calibrated RT-PCR assays quantify gene expression of human cytokines proved sensitive and specific for the investigation of cell behavior at the molecular level and the newly established CARTA software, a reliable tool for rapid data handling. Tonsil histocultures could serve as a valuable ex vivo model system for further, donor-dependent, studies on activation or repression of cytokine gene expression.
In childhood‐onset acute myeloid leukaemia (AML) the clinical value of karyotypic aberrations is now acknowledged, although there is still debate concerning the prognostic significance of some ...events. To add to this knowledge, cytogenetic analysis was performed on a consecutive series of 84 childhood AML patients diagnosed in Switzerland. A result was obtained for all patients, with 69 (82%) showing a clonal karyotypic aberration. In the remaining 15 (18%), no karyotypic aberration was seen by either conventional or fluorescence in situ hybridisation analyses. The most frequent aberrations observed were t(11q23) (19% of all patients), t(8;21) (12%) and +8 (11%). Except for cytogenetics, no clinical parameter was shown to be significantly associated with outcome. The analysis of individual cytogenetic subgroups demonstrated that aberrations involving chromosome 16q were the strongest predictor of a good prognosis, while +8 and complex karyotypes represented the strongest predictors of a poor prognosis. It was also noteworthy that patients with the rare aberrations of del(11q) (n = 4) and t(16;21)(p11;q22) (n = 3) had a poor outcome. The results support the importance of cytogenetic analysis in childhood AML, but show that further work is required in the classification of the poor prognosis aberrations.
In a pilot study, results of real-time broad-range (16S rRNA) polymerase chain reaction (PCR) performed on 45 blood samples of pediatric cancer patients with fever and neutropenia were compared with ...blood culture results.
The PCR assay used, having proven a high sensitivity in artificially spiked blood samples, was positive in only three of ten blood culture-positive samples, and it was positive in 10 of 35 (29%) culture-negative samples.
This broad-range PCR assay, which may identify not-grown bacteria potentially contributing to fever, needs improvement in sensitivity, and different reasons for positive PCR in negative blood culture samples need to be assessed before clinical application.
Background
It is unknown whether serum concentrations of mannan-binding lectin (MBL) and MBL-associated serine protease-2 (MASP-2) influence the risk of adverse events (AEs) in children with cancer ...presenting with fever in neutropenia (FN).
Methods
Pediatric patients with cancer presenting with FN after non-myeloablative chemotherapy were observed in a prospective multicenter study. Mannan-binding lectin and MASP-2 were measured using commercially available enzyme-linked immunosorbent assay in serum taken at cancer diagnosis. Multiple FN episodes per patient were allowed. Associations of MBL and MASP-2 with AE in general, with bacteremia, and with serious medical complications (SMC) during FN were analyzed using mixed logistic regression.
Results
Of 278 FN episodes, AE was reported in 84 (30%), bacteremia was reported in 42 (15%), and SMC was reported in 16 (5.8%). Median MBL was 2152 ng/mL (range, 7-10 060). It was very low (<100) in 11 (9%) patients, low (100-999) in 36 (29%) patients, and normal (≥1000) in 79 (63%) patients. Median MASP-2 was 410 ng/mL (range, 68-2771). It was low (<200) in 18 (14%) patients and normal in the remaining 108 (86%) patients. Mannan-binding lectin and MASP-2 were not significantly associated with AE or bacteremia. Normal versus low MBL was independently associated with a significantly higher risk of SMC (multivariate odds ratio, 12.8; 95% confidence interval, 1.01-163; P = .050).
Conclusions
Mannan-binding lectin and MASP-2 serum concentrations were not found to predict the risk to develop AEs or bacteremia during FN. Normal MBL was associated with an increased risk of SMC during FN. This finding, in line with earlier studies, does not support the concept of MBL supplementation in MBL-deficient children with cancer presenting with FN.
PDF
