Background: From 1983, standardized therapeutic protocols for pediatric acute myeloid leukemia (AML) based on the BFM group experience were introduced in Poland. We retrospectively analyzed the ...results of pediatric AML treatment in Poland from 1983 to 2019 (excluding promyelocytic, therapy-related, biphenotypic, and Down syndrome AML). Methods: The study included 899 children suffering from AML treated with the following: AML-PPPLBC 83 (1983–1993, n = 187), AML-PPGLBC 94 (1994–1997, n = 74), AML-PPGLBC 98 (1998–2004, n = 151), AML-BFM 2004 Interim (2004–2015, n = 356), and AML-BFM 2012 (2015–2019, n = 131). Results: The probability of three-year overall survival was 0.34 ± 0.03, 0.37 ± 0.05, 0.54 ± 0.04, 0.67 ± 0.03, and 0.75 ± 0.05; event-free survival was 0.31 ± 0.03, 0.34 ± 0.05, 0.44 ± 0.04, 0.53 ± 0.03, and 0.67 ± 0.05; and relapse-free survival was 0.52 ± 0.03, 0.65 ± 0.05, 0.58 ± 0.04, 0.66 ± 0.03, and 0.78 ± 0.05, respectively, in the subsequent periods. A systematic reduction of early deaths and deaths in remission was achieved, while the percentage of relapses decreased only in the last therapeutic period. Surprisingly good results were obtained in the group of patients treated with AML-BFM 2012 with unfavorable genetic abnormalities like KMT2A-MLLT10/t(10;11)(p12;q23) and DEK-NUP214/t(6;9)(p23;q24), while unsatisfactory outcomes were found in the patients with FLT3-ITD. Conclusions: The use of standardized, systematically modified therapeutic protocols, with the successive consideration of genetic prognostic factors, and advances in supportive care led to a significant improvement in AML treatment outcomes over the last 40 years.
Summary
For many years, T‐cell acute lymphoblastic leukaemia (T‐ALL) has been considered and treated as a single malignancy, but divergent outcomes in T‐ALL patients receiving uniform treatment ...protocols encouraged intensive research on the molecular biology of this disease. Recent findings in the field demonstrate that T‐ALL is much more heterogeneous than originally believed and extremely diverse outcomes of patients require refinement of T‐ALL classification, leading to subtype‐specific adjustment of treatment. Many different biological features of T‐ALL blast cells have recently been found to contribute to disease development and patient outcome and their analysis could potentially be introduced into improved diagnostics and classification of the disease. This review focuses on five key issues of T‐ALL biology: chromosome aberrations, gene expression profiles, gene mutations, DNA methylation patterns, and immunoglobulin/T cell receptor (Ig/TCR) gene rearrangements. Additionally, molecular monitoring of minimal residual disease, by far the most reliable independent prognostic factor in T‐ALL, has been highlighted in the context of Ig/TCR gene rearrangements. Translation of this biological information into better prognostic classification and more effective treatment should lead to improvement of outcome in T‐ALL patients.
Background:
Immune cell dysfunction is listed among complications resulting from chronic kidney disease (CKD). It could be associated with T-cells, which play a role in the lymphocytic migration and ...infiltration. However, the data on chemokine receptors expression on T-cells in patients with CKD particularly treated with peritoneal dialysis (PD) are still limited.
Methods:
The study aimed at multiparameter flow-cytometric analysis of the absolute numbers and percentage of T-cell subsets with surface chemokine receptors (CCR4, CCR5, CCR7, CXCR3, and CXCR4) or receptors’ combinations in 47 children treated with PD.
Results:
We found lower absolute numbers of total T lymphocytes, lymphocytes with surface CCR5, CXCR4+CCR5, CXCR3+CCR5 antigens and T-cells with CCR4, CCR4+CD4, CXCR3, CXCR3+CD4, and CD8 receptors. Lymphocytes T with CD4, CCR7, CD28+CCR7, CXCR3+CD8 antigens showed higher percentage in children on PD as compared to healthy children and opposite percentage values of CCR4+, CCR4+CD4+, CXCR3+ T lymphocytes were diminished. Mean fluorescent intensity for CCR7+, CCR7+CD45RO+, CCR7+CD28+, CXCR4+CD4+, CCR5+CD4+, CCR4+, CCR4+CD4+ T-cells was lower in the PD group than in healthy children. The analysis of correlation between T lymphocyte subpopulations with chemokine receptors and other parameters revealed positive correlation of CCR7+ and CCR7+CD28+ T-cells and weekly creatinine clearance, negative correlation between the percentage of CD45RO+CCR7 antigen positive T-cells and KT/Vurea.
Summary:
In conclusion, we could not confirm the phenomenon of earlier senescence of T-cells in children with CKD on PD treatment. This still requires further investigation. The higher percentage of T-cells with CCR7 surface receptor could be responsible for the increase of proliferation activity in this group of children.
This article presents the results of the analysis of data from 500 vehicle control stations concerning periodic tests of passenger cars in the number of 2 million. Based on the collected data, a ...database of vehicles has been prepared to cover technical information, such as model, mass, engine capacity and maximum power. This information has been summarized with the exploitation data such as age of the car, distance traveled, the area in which the vehicle was most frequently used, the use for business or private purposes, and intensity of operation that was measured by the ratio of kilometers traveled to the age of the car. This information constituted a set of factors affecting the reliability of the car. Information about reliability itself was the results of control tests, including occurring defects and their significance. The occurring defects were codified, which allowed their allocation to particular categories describing car systems, such as steering, braking and driving. While the significance of the fault resulted from the test result: positive (minor defects) or negative (important defects). This article presents a factor and the correlation analysis of the database, which assesses which construction and operating factors have a significant impact on damages occurring in individual car systems.
Background: The FMS-like tyrosine kinase 3 (FLT3) gene mutated in 10–15% of pediatric acute myeloid leukemia (AML) is associated with an inferior outcome. The aim of the study was to analyze the ...outcome and characteristics of FLT3-ITD-positive pediatric AML. Methods: We retrospectively analyzed the nationwide pediatric AML database from between 2005 and 2022. FLT3-ITD was found in 54/497 (10.7%) patients with available analysis. Three consecutive treatment protocols were used (AML-BFM 2004 Interim, AML-BFM 2012 Registry, AML-BFM 2019 recommendations). Results: Probabilities of 5-year overall (OS), event-free (EFS) and relapse-free survival were significantly lower in the FLT3-ITD-positive patients compared to FLT3-ITD-negative (0.54 vs. 0.71, p = 0.041; 0.36 vs. 0.59, p = 0.0004; 0.47 vs. 0.70, p = 0.0029, accordingly). An improvement in the outcome was found in the analyzed period of time, with a trend of better survival in patients treated under the AML-BFM 2012 and AML-BFM 2019 protocols compared to the AML-BFM 2004 protocol (5-year EFS 0.52 vs. 0.27, p = 0.069). There was a trend of improved outcomes in patients treated with FLT3 inhibitors (n = 9, 2-year EFS 0.67 vs. 0.33, p = 0.053) and those who received stem cell transplantation (SCT) (n = 26; 5-year EFS 0.70 vs. 0.27, p = 0.059). The co-occurrence of the WT1 mutation had a dismal impact on the prognosis (5-year EFS 0.23 vs. 0.69, p = 0.002), while the NPM1 mutation improved survival (5-year OS 1.0 vs. 0.44, p = 0.036). Conclusions: It seems that SCT and FLT3 inhibitors have a beneficial impact on the prognosis. Additional genetic alterations, like the WT1 and NPM1 mutations, significantly influence the outcome.
T‐cell acute lymphoblastic leukemia (T‐ALL) is a heterogeneous and aggressive malignancy arising from T‐cell precursors. MiRNAs are implicated in negative regulation of gene expression and when ...aberrantly expressed contribute to various cancer types, including T‐ALL. Previously we demonstrated the oncogenic potential of miR‐363‐3p overexpression in a subgroup of T‐ALL patients. Here, using combined proteomic and transcriptomic approaches, we show that miR‐363‐3p enhances cell growth of T‐ALL in vitro via inhibition of PTPRC and SOCS2, which are implicated in repression of the JAK–STAT pathway. We propose that overexpression of miR‐363‐3p is a novel mechanism potentially contributing to overactivation of JAK–STAT pathway. Additionally, by combining the transcriptomic and methylation data of T‐ALL patients, we show that promoter methylation may also contribute to downregulation of SOCS2 expression and thus potentially to JAK–STAT activation. In conclusion, we highlight aberrant miRNA expression and aberrant promoter methylation as mechanisms, alternative to mutations of JAK–STAT‐related genes, which might lead to the upregulation of JAK‐dependent signaling in T‐ALL.
The aim of the study was to retrospectively compare the effectiveness of the ALL IC-BFM 2002 and ALL IC-BFM 2009 protocols and the distribution of risk groups by the two protocols after minimal ...residual disease (MRD) measurement as well as its impact on survival. We reviewed the medical records of 3248 patients aged 1-18 years with newly diagnosed ALL who were treated in 14 hemato-oncological centers between 2002 and 2018 in Poland. The overall survival (OS) of 1872 children with ALL treated with the ALL IC 2002 protocol was 84% after 3 years, whereas the OS of 1376 children with ALL treated with the ALL IC 2009 protocol was 87% (P < 0.001). The corresponding event-free survival rates were 82% and 84% (P = 0.006). Our study shows that the ALL IC-BFM 2009 protocol improved the results of children with ALL compared to the ALL IC-BFM 2002 protocol in Poland. This analysis confirms that MRD marrow assessment on day 15 of treatment by FCM-MRD is an important predictive factor.
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy arising from T lymphocyte precursors. We have previously shown by miRNA-seq, that miRNAs from the mir-106a-363 cluster are ...overexpressed in pediatric T-ALL. In silico analysis indicated their potential involvement in the regulation of apoptosis. Here, we aimed to test the hypothesis on the pro-tumorigenic roles of these miRNAs in T-ALL cells in vitro. We demonstrate, for the first time, that hsa-miR-20b-5p and hsa-miR-363-3p from the mir-106a-363 cluster, when upregulated in T-ALL cells in vitro, protect leukemic cells from apoptosis, enhance proliferation, and contribute to growth advantage. We show, using dual luciferase reporter assays, Ago2-RNA immunoprecipitation, RT-qPCR, and Western blots, that the oncogenic effects of these upregulated miRNAs might, at least in part, be mediated by the downregulation of two important tumor suppressor genes,
and
, targeted by both miRNAs. Additionally, we demonstrate the cooperative effects of these two miRNAs by simultaneous inhibition of both miRNAs as compared to the inhibition of single miRNAs. We postulate that hsa-miR-20b-5p and hsa-miR-363-3p from the mir-106a-363 cluster might serve as oncomiRs in T-ALL, by contributing to post-transcriptional repression of key tumor suppressors,
and
.
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