Minimal residual disease assessment in transplant-eligible patients with multiple myeloma: real-world applications of multiparametric flow cytometry-DURAClone (CAREMM-2104).

Not available.

Genomic insights into inherited bone marrow failure syndromes in a Korean population.

Inherited bone marrow failure syndromes (IBMFS) pose significant diagnostic challenges due to overlapping symptoms and variable expressivity, despite evolving genomic insights. The study aimed to elucidate the genomic landscape among 130 Korean patients with IBMFS. We conducted targeted next-generation sequencing (NGS) and clinical exome sequencing (CES) across the cohort, complemented by whole genome sequencing (WGS) and chromosomal microarray (CMA) in 12 and 47 cases, respectively, with negative initial results. Notably, 50% (n = 65) of our cohort achieved a genomic diagnosis. Among these, 35 patients exhibited mutations associated with classic IBMFSs (n = 33) and the recently defined IBMFS, aplastic anaemia, mental retardation and dwarfism syndrome (AmeDS, n = 2). Classic IBMFSs were predominantly detected via targeted NGS (85%, n = 28) and CES (88%, n = 29), whereas AMeDS was exclusively identified through CES. Both CMA and WGS aided in identifying copy number variations (n = 2) and mutations in previously unexplored regions (n = 2). Additionally, 30 patients were diagnosed with other congenital diseases, encompassing 13 distinct entities including inherited thrombocytopenia (n = 12), myeloid neoplasms with germline predisposition (n = 8), congenital immune disorders (n = 7) and miscellaneous genomic conditions (n = 3). CES was particularly effective in revealing these diverse diagnoses. Our findings underscore the significance of comprehensive genomic analysis in IBMFS, highlighting the need for ongoing exploration in this complex field.

The Inhibition Activity of Natural Methoxyflavonoid from Inula britannica on Soluble Epoxide Hydrolase and NO Production in RAW264.7 Cells.

Soluble epoxide hydrolase (sEH) is an enzyme targeted for the treatment of inflammation and cardiovascular diseases. Activated inflammatory cells produce nitric oxide (NO), which induces oxidative stress and exacerbates inflammation. We identify an inhibitor able to suppress sEH and thus NO production. Five flavonoids 1-5 isolated from Inula britannica flowers were evaluated for their abilities to inhibit sEH with IC50 values of 12.1 ± 0.1 to 62.8 ± 1.8 µM and for their effects on enzyme kinetics. A simulation study using computational chemistry was conducted as well. Furthermore, five inhibitors (1-5) were confirmed to suppress NO levels at 10 µM. The results showed that flavonoids 1-5 exhibited inhibitory activity in all tests, with compound 3 exhibiting the most significant efficacy. Thus, in the development of anti-inflammatory inhibitors, compound 3 is a promising natural candidate.

Analytical Performance Evaluation of a Digital Real-Time PCR for Quantifying Major BCR::ABL1 Transcripts.

BACKGROUND: Accurate quantification of the BCR::ABL1 transcripts is essential for measurable residual disease (MRD) monitoring in chronic myeloid leukemia (CML) after tyrosine kinase inhibitor (TKI) treatment. This study evaluated the newly developed digital real-time PCR method, Dr. PCR, as an alternative reverse transcription-PCR (qRT-PCR) for MRD detection. METHODS: The performance of Dr. PCR was assessed using reference and clinical materials. Precision, linearity, and correlation with qRT-PCR were evaluated. MRD levels detected by Dr. PCR were compared with qRT-PCR, and practical advantages were investigated. RESULTS: Dr. PCR detected MRD up to 0.0032%IS (MR4.5) with excellent precision and linearity and showed a strong correlation with qRT-PCR results. Notably, Dr. PCR identified higher levels of MRD in 12.7% (29/229) of patients than qRT-PCR, including six cases of MR4, which is a critical level for TKI discontinuation. Dr. PCR also allowed for sufficient ABL1 copies in all cases, while qRT-PCR necessitated multiple repeat tests in 3.5% (8/229) of cases. CONCLUSION: Our study provides a body of evidence supporting the clinical application of Dr. PCR as a rapid and efficient method for assessing MRD in patients with CML under the current treatment regimen.

Clinical significance of decreased or loss of ABO blood group expression in acute myeloid leukaemia: A single-centre retrospective study.

BACKGROUND AND OBJECTIVES: Decreased or loss of ABO blood group antigen expression has been observed in acute myeloid leukaemia (AML) patients. We studied the clinical significance of this group in AML patients. MATERIALS AND METHODS: This was a retrospective, single-centre cohort study in which the data were retrieved from April 2009 to December 2019. A total of 1592 AML patients with normal ABO blood group antigen (Group I) and 65 patients of decreased or loss of ABO blood group antigen (Group II) group were enrolled. Data were collected at the time of initial admission for pathological diagnosis. To interrogate the underlying mechanism, publicly available The Cancer Genome Atlas AML data were downloaded. RESULTS: Group II consisted of 3.9% (65/1657) of AML patients. The 90-day survival (D90) probability was higher for Group II with a mean survival of 86.4 days compared to 80.6 days for Group I (p = 0.047). Group II had higher haematocrit (28.6 vs. 27.4%) and lower d-dimer, fibrinogen degradation production and C-reactive protein. Publicly available data revealed that among 11 CpG methylation sites within the ABO gene, 4 sites with elevated methylation level were associated with improved D90 survival probability and demonstrated an inverse correlation with ABO gene expression. Lower expression of the ABO gene showed improved survival trends for D90 (p = 0.058) and 180-day survival (p = 0.072). CONCLUSION: AML with decreased expression or loss of ABO blood group showed better early survival during D90. Transfusion support for this subgroup of AML patients should be meticulously performed considering serum typing.

Analytical performance of the Abbott ID NOW 2.0 assay for SARS-CoV-2 detection in clinical samples from symptomatic patients.

We evaluated the analytical performance of ID NOW™ COVID-19 2.0 assay versus conventional real-time reverse transcription-polymerase chain reaction (RT-PCR) using a total of 792 clinical samples from nasopharyngeal and oropharyngeal swabs, stored in frozen universal transport medium samples. Positive percent agreement (PPA) and negative percent agreement of ID NOW were 97.6 % and 100 %, respectively. The overall percent agreement between ID NOW and RT-PCR was 99.5 %. The PPA of ID NOW in detecting SARS-CoV-2 in 164 RT-PCR positive patients, all of whom had symptoms related COVID-19, was 97.1 % within 8 days since symptom onset, 97.9 % from 8 to 14 days since symptom onset, and 97.6 % after 14 days since symptom onset, with no significant difference between the days since symptom onset. The ID NOW assay demonstrated good performance, providing a rapid and randomly accessible alternative to conventional RT-PCR for timely SARS-CoV-2 detection, particularly in situations requiring rapid results for patient care.