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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 -
Therapeutic Advances in Hematology 2024Clonal cytopenia of undetermined significance (CCUS) has the characteristics of high-risk transformation into myelodysplastic syndromes. At present, there are few...
Rapid and sustained response to luspatercept and eltrombopag combined treatment in one case of clonal cytopenias of undetermined significance with prior failure to cyclosporin and androgen therapy: a case report.
Clonal cytopenia of undetermined significance (CCUS) has the characteristics of high-risk transformation into myelodysplastic syndromes. At present, there are few effective treatments for CCUS, and there is no consensus or evidence-based recommendation. We present a case demonstrating a rapid, significant and sustained response to combined treatment with luspatercept and eltrombopag, following the failure of cyclosporin and androgen therapy. Even after discontinuing luspatercept for 10 months, trilineage haematopoiesis remained normal with the use of cyclosporin and other haematopoietic stimulants. This case suggests that the inhibition of transforming growth factor-β could potentially have an immunomodulatory effect, thereby promoting the recovery of haematopoietic function. Luspatercept, along with Acalabrutinib or Cyclosporine, may synergistically stimulate haematopoiesis.
PubMed: 38911444
DOI: 10.1177/20406207241260353 -
Cureus May 2024Vitamin B12 deficiency is a common condition that is often asymptomatic, though in severe cases may cause megaloblastic anemia and even neurologic symptoms....
Vitamin B12 deficiency is a common condition that is often asymptomatic, though in severe cases may cause megaloblastic anemia and even neurologic symptoms. Occasionally, the clinical presentation can include pancytopenia and thus mimic a more concerning myelodysplastic syndrome (MDS) until corrected by B12 supplementation. In this unusual case, we present a patient with B12 deficiency who presents with severe macrocytic anemia, neutropenia, lymphocytosis, and a bone marrow morphology consistent with MDS.
PubMed: 38910768
DOI: 10.7759/cureus.60837 -
Familial Cancer Jun 2024Fanconi anemia (FA) is an inherited bone marrow failure syndrome (IBMFS) characterized by pathogenic variants in the FA/BRCA DNA repair pathway genes. Individuals with...
Fanconi anemia (FA) is an inherited bone marrow failure syndrome (IBMFS) characterized by pathogenic variants in the FA/BRCA DNA repair pathway genes. Individuals with FA have an elevated risk of developing myelodysplastic syndrome, acute myeloid leukemia, and solid tumors. Hematopoietic cell transplantation (HCT) is the most effective treatment for FA related bone marrow failure but can increase the risk of cancer development. Information on benign tumors and NMSC is lacking in patients with FA. Our objective was to characterize patients with FA enrolled in the National Cancer Institute IBMFS Study who have experienced non-melanoma skin cancers (NMSC) and/or benign tumors (BT). A total of 200 patients diagnosed with FA were enrolled in the Institutional Review Board approved study "Etiologic Investigation of Cancer Susceptibility in IBMFS: A Natural History Study" (NCT00027274). Through medical records review, we identified 30 patients with at least one NMSC, either squamous or basal cell carcinoma, or benign tumor. The remaining 170 patients comprised the control group. Out of 200 patients, 12 had NMSC, 25 had benign tumors, with an age range of 11-64 and 0-56 years, respectively. The median age at HCT was 30.5 years for NMSC patients, 9 years for benign tumor patients, and 9.1 years for controls. The most common genotype observed was FANCA, followed by FANCC and FANCI. Benign tumors spanned diverse anatomical locations. Early onset NMSC in patients with FA compared to the general population emphasizes the need for consistent monitoring in patients with FA, while the diverse anatomical locations of benign tumors underscore the importance of comprehensive surveillance for timely interventions in managing symptomatology and heightened cancer risk.
PubMed: 38907138
DOI: 10.1007/s10689-024-00410-2 -
Journal of the American Academy of... Jun 2024
Review
PubMed: 38906261
DOI: 10.1016/j.jaad.2024.05.086 -
Journal of Chromatography. B,... Jun 2024Decitabine is a DNA methyltransferase inhibitor used in the treatment of acute myeloid leukemia and myelodysplastic syndrome. The notion that ongoing trials are...
Decitabine is a DNA methyltransferase inhibitor used in the treatment of acute myeloid leukemia and myelodysplastic syndrome. The notion that ongoing trials are presently exploring the combined use of decitabine, with or without the cytidine deaminase inhibitor cedazuridine, and other antileukemic drugs necessitates a comprehensive understanding of pharmacokinetic properties and an evaluation of drug-drug interaction liabilities. We report here the development and validation of a sensitive UHPLC-MS/MS method for quantifying decitabine in mouse plasma, which should be useful for such studies. The method involved a one-step protein precipitation extraction, and chromatographic separation on an XBridge HILIC column using gradient elution. The method was found to be robust, accurate, precise, and sufficiently sensitive (lower limit of quantitation, 0.4 ng/mL) to determine decitabine concentrations in microvolumes of plasma from mice receiving the agent orally or intravenously in the presence or absence of cedazuridine.
PubMed: 38905720
DOI: 10.1016/j.jchromb.2024.124209