Developmental maturation of the hematopoietic system controlled by a Lin28b-let-7-PRC1 axis

Hematopoiesis changes over life to meet the demands of maturation and aging. Here, we find that the definitive hematopoietic stem and progenitor cell (HSPC) compartment is remodeled from gestation into adulthood, a process regulated by the heterochronic Lin28b/let-7 axis. Native fetal and neonatal HSPCs distribute with a pro-lymphoid/erythroid bias with a shift toward myeloid output in adulthood. By mining transcriptomic data comparing juvenile and adult HSPCs and reconstructing coordinately activated gene regulatory networks, we uncover the Polycomb repressor complex 1 (PRC1) component Cbx2 as an effector of Lin28b/let-7 control of hematopoietic maturation. We find that juvenile Cbx2-/- hematopoietic tissues show impairment of B-lymphopoiesis and a precocious adult-like myeloid bias and that Cbx2/PRC1 regulates developmental timing of expression of key hematopoietic transcription factors. These findings define a novel mechanism of epigenetic regulation of HSPC output as a function of age with potential impact on age-biased pediatric and adult blood disorders.

Herbal Medication of Recurrent Aphthous Stomatitis: A Narrative Review

A mouth ulcer or recurrent aphthous stomatitis (RAS) is a mouth mucous tissue inflammation. This disease mainly occurs in patients 10-40 years of age, preferably in women and high socioeconomic backgrounds. The cause of mouth ulcers or RAS could be trauma, infection, digestive problems, or blood disorders. Herbal practitioners widely use herbs, folks, and society to treat various diseases. This research aimed to describe the herbal treatment for RAS. The review results show there are nine plants with the ability to cure RAS, they are Persea americana Mill., Averrhoa bilimbi L., Abrus precatorius Linn., Camellia sinensis (L.) Kuntze., Psidium guajava L., Kaempferia galanga Linn., Aloe vera, Curcuma longa and Citrus hystrix DC. The most parameters used in the studies are clinical trials and in vitro tests.

Discovery of clinically relevant fusions in pediatric cancer

Background Pediatric cancers typically have a distinct genomic landscape when compared to adult cancers and frequently carry somatic gene fusion events that alter gene expression and drive tumorigenesis. Sensitive and specific detection of gene fusions through the analysis of next-generation-based RNA sequencing (RNA-Seq) data is computationally challenging and may be confounded by low tumor cellularity or underlying genomic complexity. Furthermore, numerous computational tools are available to identify fusions from supporting RNA-Seq reads, yet each algorithm demonstrates unique variability in sensitivity and precision, and no clearly superior approach currently exists. To overcome these challenges, we have developed an ensemble fusion calling approach to increase the accuracy of identifying fusions. Results Our Ensemble Fusion (EnFusion) approach utilizes seven fusion calling algorithms: Arriba, CICERO, FusionMap, FusionCatcher, JAFFA, MapSplice, and STAR-Fusion, which are packaged as a fully automated pipeline using Docker and Amazon Web Services (AWS) serverless technology. This method uses paired end RNA-Seq sequence reads as input, and the output from each algorithm is examined to identify fusions detected by a consensus of at least three algorithms. These consensus fusion results are filtered by comparison to an internal database to remove likely artifactual fusions occurring at high frequencies in our internal cohort, while a “known fusion list” prevents failure to report known pathogenic events. We have employed the EnFusion pipeline on RNA-Seq data from 229 patients with pediatric cancer or blood disorders studied under an IRB-approved protocol. The samples consist of 138 central nervous system tumors, 73 solid tumors, and 18 hematologic malignancies or disorders. The combination of an ensemble fusion-calling pipeline and a knowledge-based filtering strategy identified 67 clinically relevant fusions among our cohort (diagnostic yield of 29.3%), including RBPMS-MET, BCAN-NTRK1, and TRIM22-BRAF fusions. Following clinical confirmation and reporting in the patient’s medical record, both known and novel fusions provided medically meaningful information. Conclusions The EnFusion pipeline offers a streamlined approach to discover fusions in cancer, at higher levels of sensitivity and accuracy than single algorithm methods. Furthermore, this method accurately identifies driver fusions in pediatric cancer, providing clinical impact by contributing evidence to diagnosis and, when appropriate, indicating targeted therapies.

Wstępna diagnostyka chorób krwi

Final result of treatment of majority of neoplastic and non‑neoplastic blood disorders depends on their early diagnosis and immediate referral to hematologist. This determines that initial hematological diagnosis has to be carried out on the level of family physician or other doctor, who in the process of diagnosis of other disorder will detect abnormalities that may suggest a blood disorder. Current article concerns the use of a triad of laboratory tests: complete blood count, erythrocyte sedimentation rate, and urine analysis. Borderline values are provided that should prompt referral to a hematologist, and it is explained why these particular values were accepted. Common use of such information should shorten time from initial symptoms of blood disorders to the beginning of therapy.

A Novel Algorithm Using Cell Population Data (VCS Parameters) as a Screening Discriminant between Alpha and Beta Thalassemia Traits

Thalassemia is one of the major inherited haematological disorders in the Southeast Asia region. This study explored the potential utility of red blood cell (RBC) parameters and reticulocyte cell population data (CPD) parameters in the differential diagnosis of α and β-thalassaemia traits as a rapid and cost-effective tool for screening of thalassemia traits. In this study, a total of 1597 subjects (1394 apparently healthy subjects, 155 subjects with α-thalassaemia trait, and 48 subjects with β-thalassaemia trait) were accrued. The parameters studied were the RBC parameters and reticulocyte CPD parameters derived from Unicel DxH800. A novel algorithm named αβ-algorithm was developed: (MN-LMALS-RET × RDW) − MCH) to discriminate α from β-thalassaemia trait with a cut-off value of 1742.5 [AUC = 0.966, sensitivity = 92%, specificity = 90%, 95% CI = 0.94–0.99]. Two prospective studies were carried: an in-house cohort to assess the specificity of this algorithm in 310 samples comprising various RBC disorders and in an interlaboratory cohort of 65 α-thalassemia trait, and 30 β-thalassaemia trait subjects to assess the reproducibility of the findings. We propose the αβ-algorithm to serve as a rapid, inexpensive surrogate evaluation tool of α and β-thalassaemia in the population screening of thalassemia traits in geographic regions with a high burden of these inherited blood disorders.

Barriers to Adherence to Iron Chelation Therapy in Thalassemia Patients

Background: Thalassemias are the most common inheritable blood disorders requiring regular blood transfusions and iron chelating therapy. Non-adherence to iron chelation therapy increases complications and is a problem in treating thalassemia. To assess the reasons of non-adherence to iron chelating drug in treating thalassemia. Materials and methods: This descriptive cross-sectional study was carried out in the thalassemia ward of Chattogram Maa Shishu-O-General Hospital, Chattogram from July, 2013 to June, 2014. 70 thalassemia patients aged 2-18 years previously treated with iron chelating drugs were included. Parents were interviewed according to a formulated questionnaire based on discontinuation of iron chelating drugs and its reasons. Data were analyzed by both manually and by SPSS-18. Results: About 48.6% patients needed blood transfusion >10 units/year and 62.9% patients were prescribed with iron chelating drugs. Near about half patients (47.7%) did not continued iron chelating therapy till full prescribed period. Deferiprone (31.8%) and combination of deferipronc & desferrioxamine (31.8%) was the most commonly prescribed drug. Deferiprone is the drug to which most of the patients (70%) were adherent and a good number of patients (65%) discontinued desferrioxamine. Financial problem (100%) was the only reason for discontinuation of oral chelator. In case of parenteral chelator, besides finanacial problem (38.5%), time consuming natures (38.5%), need of hospital admission (23%) are the other causes for non-adherence to iron chelation therapy. Conclusion: Financial problem is the main cause of non-adherence to iron chelation therapy. Iron chelating drugs should be available at low cost. Chatt Maa Shi Hosp Med Coll J; Vol.20 (2); July 2021; Page 45-49

Gene therapy and editing in the treatment of hereditary blood disorders: Medical and ethical aspects

Gene therapy and gene editing are revolutionising the treatment of genetic diseases, most notably haematological disorders. This paper evaluates the use of both techniques in hereditary blood disorders. Many studies have been conducted in this field, especially with gene therapy, with very promising results in diseases such as haemophilia, certain haemoglobinopathies and Fanconi anaemia. The application of these techniques in clinical practice and the foreseeable development of these approaches in the coming years suggest that it might be useful to evaluate the results achieved thus far. It is also essential to reflect on the possible bioethical concerns raised by the use of both techniques, especially in terms of safety issues for patients, potential side effects, treatment duration, accessibility and cost of treatment, and the heritability of genetic changes produced if germline cells are used.