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Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To investigate the expression level and clinical correlation of gene cluster () in different types of anemia.
OBJECTIVE
To investigate the expression level and clinical correlation of gene cluster () in different types of anemia.
METHODS
The peripheral blood of patients with aplastic anemia (AA), myelodysplastic syndrome (MDS) and diffuse large B-cell lymphoma (DLBCL) who had been diagnosed with anemia for the first time and after chemotherapy were collected. The expression levels of and were measured by RT-qPCR, and the correlation between the expression levels of and and routine laboratory indexes was analyzed by Spearman correlation analysis.
RESULTS
The expression levels of and in the peripheral blood of AA and MDS patients were significantly lower than those in normal controls (all < 0.01). No statistical differences were observed in the expression level of in three subgroups of DLBCL patients ( >0.05), while the expression level of in peripheral blood of three subgroups of DLBCL patients were significantly higher than those in normal controls (all < 0.05). Correlation analysis showed that the expression levels of and in AA patients were positively correlated with red blood cell distribution width-coefficient of variation (RDW-CV) ( =0.629, 0.574). There were no significant correlations between the expression levels of and and laboratory parameters in MDS and DLBCL patients.
CONCLUSION
Different types of anemia disorders have varying levels of and expression, which is anticipated to develop into a secondary diagnostic and differential diagnostic indicator for clinical anemia diseases.
Topics: Humans; MicroRNAs; Myelodysplastic Syndromes; Lymphoma, Large B-Cell, Diffuse; Anemia, Aplastic; Anemia; Multigene Family
PubMed: 38926974
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.026 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To investigate the clinical significance of allelic state in patients with myelodysplastic syndromes (MDS).
OBJECTIVE
To investigate the clinical significance of allelic state in patients with myelodysplastic syndromes (MDS).
METHODS
The clinical data of 858 MDS patients who underwent second-generation sequencing (NGS) testing in the First Affiliated Hospital of Soochow University from January 2019 to December 2021 were retrospectively analyzed.
RESULTS
The median age of the patients was 52 years old, and median follow-up time was 23.8 (0.4-109.6) months. Four hundred and one patients (46.7%) had at least one chromosomal abnormality, including 106 complex karyotypes and 78 monosomal karyotypes. A total of 103 cases of mutations were identified, with a mutation rate of 12%. Compared with wild-type, various types of chromosomal abnormalities were significantly more common in patients with mutations (all < 0.001). Patients with mutations had lower hemoglobin levels, lower platelet counts and higher percentage of bone marrow primitive cell compared with wild type (all < 0.05), and significantly shorter overall survival (OS). Among 97 evaluable patients, 33 cases (34%) were mono-allelic mutation, while 64 cases were bi-allelic mutation. Patients in bi-allelic mutation subgroup had a higher proportion of chromosomal abnormalities and a lower number of co-mutations compared with mono-allelic mutation. The median OS was 33.6 months in patients with mono-allelic state and only 11.4 months in patients with bi-allelic state (=2.138, 95% : 1.053-4.343, >0.05). Median OS was not reached in wild-type patients, and there was a significant difference in OS among wild-type, mono-allelic and bi-allelic mutation patients ( < 0.001). Multivariable Cox regression analysis showed that bi-allelic was an independent predictor of poor outcomes (=2.808, 95% : 1.487-5.003, =0.001), while mono-allelic mutation and wild-type were not.
CONCLUSION
Patients with mutations have a poor prognosis, and bi-allelic mutations have a worse prognosis compared with mono-allelic mutations and independently affect the prognosis of MDS patients.
Topics: Humans; Myelodysplastic Syndromes; Middle Aged; Prognosis; Retrospective Studies; Tumor Suppressor Protein p53; Mutation; Alleles; Chromosome Aberrations; Male; Female
PubMed: 38926972
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.024 -
Discovery Medicine Jun 2024Genetic mutations play a crucial role in the development and progression of myelodysplastic syndromes (MDS), impacting the immune microenvironment and influencing the...
BACKGROUND
Genetic mutations play a crucial role in the development and progression of myelodysplastic syndromes (MDS), impacting the immune microenvironment and influencing the choice of treatment regimen, as well as the efficacy and prognosis of patients. The objective of this study was to examine variations in hematological and immunological characteristics associated with common gene mutations in MDS patients and establish a foundation for the precise treatment of MDS.
METHODS
The hematological, immunological, and other clinical features of 71 recently diagnosed MDS patients from January 1, 2019, to July 31, 2023, were retrospectively analyzed. These patients were categorized based on their gene mutations, and the variances in hematological and immunological characteristics among distinct groups were compared.
RESULTS
Hematological variances were observed among different gene mutation groups. Specifically, platelet counts in the splicing factor 3B subunit 1 () mutation group were notably higher compared to the wild-type group ( = 0.009). Conversely, in the additional sex combs like 1 () mutation groups, monocyte ratios were significantly elevated in comparison to the wild-type group ( = 0.046), and in the ten-eleven translocation 2 () mutation group, lymphocyte ratios were significantly lower ( = 0.022). Additionally, the leukocyte ( = 0.005), neutrophil ratio ( = 0.002), and lymphocyte ratio ( = 0.001) were significantly higher in the Runt-related transcription factor 1 () mutation group. Regarding immunological distinctions, the Natural Killer (NK) cell ratio demonstrated a significant increase in the mutation group ( = 0.005). Moreover, the mutation group exhibited a significantly higher Interleukin-8 (IL-8) level ( = 0.017). In contrast, the U2 small nuclear RNA auxiliary factor 1 () group displayed significantly lower levels of IL-1β ( = 0.033), IL-10 ( = 0.033), and Tumour Necrosis Factor-α (TNF-α) ( = 0.009).
CONCLUSION
Distinct variations exist in the immune microenvironment of MDS associated with different genetic mutations. Further studies are imperative to delve into the underlying mechanisms that drive these differences.
Topics: Humans; Myelodysplastic Syndromes; Mutation; Female; Male; Middle Aged; Aged; RNA Splicing Factors; Retrospective Studies; Adult; Dioxygenases; Aged, 80 and over; DNA-Binding Proteins; Phosphoproteins; Killer Cells, Natural; Core Binding Factor Alpha 2 Subunit; Platelet Count; Repressor Proteins
PubMed: 38926115
DOI: 10.24976/Discov.Med.202436185.119 -
Hamostaseologie Jun 2024This review summarizes the rationale and current data on the use of thrombopoietin receptor agonists (TPO-RAs) for treating severe thrombocytopenia in infants, children,...
This review summarizes the rationale and current data on the use of thrombopoietin receptor agonists (TPO-RAs) for treating severe thrombocytopenia in infants, children, and adolescents. It focuses on substances that have been approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) for pediatric patients. Romiplostim and eltrombopag are already established as second-line treatment for persistent or chronic immune thrombocytopenia (ITP). As in adults, TPO-RAs are currently also evaluated in severe aplastic anemia (SAA), chemotherapy-induced thrombocytopenia (CIT), myelodysplastic syndromes (MDS), and poor engraftment after hematopoietic stem cell transplantation in pediatric and adolescent patients. Moreover, studies on the implication of TPO-RA in treating rare inherited thrombocytopenias, such as Wiskott-Aldrich syndrome (WAS), congenital amegakaryocytic thrombocytopenia (CAMT), or -associated thrombocytopenia, deserve future attention. Current developments include testing of avatrombopag and lusutrombopag that are approved for the treatment of thrombocytopenia associated with chronic liver disease (CLD) in adult patients. In pediatric and adolescent medicine, we expect in the near future a broader use of TPO-RAs as first-line treatment in primary ITP, thereby considering immunomodulatory effects that increase the rate of sustained remission off-treatment, and a selective use in rare inherited thrombocytopenias based on current clinical trials.
PubMed: 38925157
DOI: 10.1055/a-2247-4209 -
Clinical and Translational Medicine Jul 2024
Topics: Humans; Hemoglobinuria, Paroxysmal; Single-Cell Analysis; Cell Differentiation; Hematopoietic Stem Cells; Male; Female; Bone Marrow Cells; Adult
PubMed: 38924689
DOI: 10.1002/ctm2.1671 -
Current Osteoporosis Reports Jun 2024Along with a strong impact on skeletal integrity, bone marrow adipose tissue (BMAT) is an important modulator of the adult hematopoietic system. This review will... (Review)
Review
PURPOSE OF REVIEW
Along with a strong impact on skeletal integrity, bone marrow adipose tissue (BMAT) is an important modulator of the adult hematopoietic system. This review will summarize the current knowledge on the causal relationship between bone marrow (BM) adipogenesis and the development and progression of hematologic malignancies.
RECENT FINDINGS
BM adipocytes (BMAds) support a number of processes promoting oncogenesis, including the evolution of clonal hematopoiesis, malignant cell survival, proliferation, angiogenesis, and chemoresistance. In addition, leukemic cells manipulate surrounding BMAds by promoting lipolysis and release of free fatty acids, which are then utilized by leukemic cells via β-oxidation. Therefore, limiting BM adipogenesis, blocking BMAd-derived adipokines, or lipid metabolism obstruction have been considered as potential treatment options for hematological malignancies. Leukemic stem cells rely heavily on BMAds within the structural BM microenvironment for necessary signals which foster disease progression. Further development of 3D constructs resembling BMAT at different skeletal regions are critical to better understand these relationships in geometric space and may provide essential insight into the development of hematologic malignancies within the BM niche. In turn, these mechanisms provide promising potential as novel approaches to targeting the microenvironment with new therapeutic strategies.
PubMed: 38922359
DOI: 10.1007/s11914-024-00879-x -
Current Oncology (Toronto, Ont.) May 2024On behalf of Cell Therapy Transplant Canada (CTTC), we are pleased to present the Abstracts of the CTTC 2023 Annual Conference. The conference was held in-person, 31...
On behalf of Cell Therapy Transplant Canada (CTTC), we are pleased to present the Abstracts of the CTTC 2023 Annual Conference. The conference was held in-person, 31 May-2 June 2023, in Halifax, Nova Scotia at the Westin Nova Scotian hotel. Poster authors presented their work during a lively and engaging welcome reception on Thursday, 1 June, and oral abstract authors were featured during the oral abstract session in the afternoon of Friday, 2 June 2023. Twenty-three (23) abstracts were selected for presentation as posters and four (4) as oral presentations. Abstracts were submitted within four categories: (1) Basic/Translational Sciences, (2) Clinical Trials/Observations, (3) Laboratory/Quality, and (4) Pharmacy/Nursing/Other Transplant Support. The top four (4) oral abstracts and top four (4) poster abstracts were selected to receive an award. All of these were marked as "Award Recipient" within the relevant category. We congratulate all the presenters on their research and contributions to the field.
PubMed: 38920707
DOI: 10.3390/curroncol31060223 -
Reumatologia Clinica Jun 2024VEXAS syndrome is a rare entity secondary to UBA1 gene mutations, located on the X chromosome. This mutation generates, as a consequence, a characteristic vacuolation on...
VEXAS syndrome is a rare entity secondary to UBA1 gene mutations, located on the X chromosome. This mutation generates, as a consequence, a characteristic vacuolation on haematopoietic stem-cells. It is characterized by multiple autoinflammatory and haematologic manifestations, which respond and end up being dependent on corticosteroid treatment. In this publication we present a 2-case series diagnosed at our hospital and make a brief literature review of the published evidence so far.
PubMed: 38918162
DOI: 10.1016/j.reumae.2024.05.006 -
International Immunopharmacology Jun 2024The capacity of T cells to initiate anti-leukemia immune responses is determined by the ability of their receptors (TCRs) to recognize leukemia neoantigens. Epigenetic...
The capacity of T cells to initiate anti-leukemia immune responses is determined by the ability of their receptors (TCRs) to recognize leukemia neoantigens. Epigenetic mechanisms including DNA methylation contribute to shaping the TCR repertoire composition and diversity. The DNA hypomethylating agents (HMAs) have been widely used in the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Whether DNA HMAs directly influence TCR gene loci methylation patterns remains unknown. By analyzing public datasets, we compared methylation patterns across TCR loci in AML patients and healthy controls. We also explored how HMAs influence TCR loci DNA methylation in patients with AML. While methylation patterns are largely conserved across the TCR loci, certain V genes exhibit high interindividual variability. Although overall methylation levels within the TCR loci did not show significant differences, specific sites, including 32 TRAV and 12 TRBV sites exhibited distinct methylation patterns when comparing T cells from healthy donors to those from patients with AML. In leukemic cells, decitabine treatment demethylates sites across the TRAV and TRBV genes. While not as significant, a similar pattern of demethylation is observed in T cells. Pretreatment AML samples exhibit higher methylation beta values in differentially methylated positions (DMPs) compared with non-DMPs. Methylation levels of certain TRAV and TRBV genes in leukemic cells are associated with patients' risk status. The presence of disease specific TCR loci methylated signatures that are associated with clinical outcome presents an opportunity for therapeutic intervention. HMAs can modulate the TCR loci methylation patterns, yet whether they could reprogram the TCR repertoire composition remains to be explored.
PubMed: 38917523
DOI: 10.1016/j.intimp.2024.112376 -
Archives of Public Health = Archives... Jun 2024Oncological home hospitalization (HH) was implemented in a Belgian context to evaluate the feasibility of oncological HH. In a first HH model (HH1), implemented by three...
BACKGROUND
Oncological home hospitalization (HH) was implemented in a Belgian context to evaluate the feasibility of oncological HH. In a first HH model (HH1), implemented by three Belgian hospitals, two home nursing organizations and a grouping of independent nurses, the blood draw and monitoring prior to intravenous therapy was performed by a trained home nurse at the patient's home the day before the visit to the day hospital. In a second HH model (HH2), implemented in one hospital, the administration of two subcutaneous treatments (Azacitidine and Bortezomib) for myelodysplastic syndrome and multiple myeloma were provided at home instead of in the hospital. A previous study on this pilot showed that oncological HH is feasible and safe and improves the Quality of Life. The aim of this study is to investigate the cost and reimbursement of cancer treatment in these two HH models compared to the Standard of Care (SOC).
METHODS
A bottom-up micro-costing study was conducted to compare the costs and revenues for the providers (hospitals and home care organizations) of the SOC and the HH models.
RESULTS
Costs associated to HH were higher than the SOC in the hospital. Comparing revenues with costs, the research revealed that the reimbursement from the National Health Insurance of HH for oncological patients is insufficient. In HH1, costs were higher than in the SOC (+ €50.4). There was a reduction in costs in the hospital by moving the blood draw to the home setting (-€23.9), but the costs in home care were higher (+ €74.3). The extra revenues in home care (+ €33.6) were insufficient to cover the costs. The cost difference between the SOC and HH2 (+ €9.5 for Azacetidine) was smaller than in HH1. But, there was almost no funding for subcutaneous administration in home care. If the product is administered in a day hospital, the hospital receives a revenue of €124 per administration, while in home care the funding is €5 per visit.
CONCLUSION
Costs of HH are higher and the reimbursement from Belgian NHI is insufficient to organize HH. As a result, HH for oncology patient is still limited in Belgium.
PubMed: 38915071
DOI: 10.1186/s13690-024-01317-1