Homozygous Southeast Asian Ovalocytosis in five live-born neonates.

Not available.

The BRCA1 and BRCA2 Genes in Early-Onset Breast Cancer Patients.

Approximately 5-10% of breast cancers are attributable to genetic susceptibility. Mutations in the BRCA1 and BRCA2 genes are the best known genetic factors to date. The goal of this study was to determine the structure and distribution of haplotypes of the BRCA1 and BRCA2 genes in early-onset breast cancer patients. We enrolled 70 patients diagnosed with early-onset breast cancer. A total of 21 SNPs (11 on BRCA1 and 10 on BRCA2) and 1 dinucleotide deletion on BRCA1 were genotyped using nested allele-specific PCR methods. Linkage disequilibrium (LD) analysis was conducted, and haplotypes were deduced from the genotype data. Two tightly linked LD blocks were observed on each of the BRCA1 and BRCA2 genes. Variant-free haplotypes (TAT-AG for BRCA1 and ATA-AAT for BRCA2) were observed at a frequency of more than 50% on each gene along with variable frequencies of derived haplotypes. The variant 3'-subhaplotype CGC displayed strong LD with 5'-subhaplotypes GA, AA, and GG on BRCA1 gene. Haplotypes ATA-AGT, ATC-AAT, and ATA-AAC were the variant haplotypes frequent on BRCA2 gene. Although the clinical significance of these derived haplotypes has not yet been established, it is expected that some of these haplotypes, especially the less frequent subhaplotypes, eventually will be shown to be indicative of a predisposition to early-onset breast cancer.

Human mesenchymal stem cells promote CD34+ hematopoietic stem cell proliferation with preserved red blood cell differentiation capacity.

Studies showed that co-transplantation of mesenchymal stem cells (MSCs) and cord blood-derived CD34+ hematopoietic stem cells (HSCs) offered greater therapeutic effects but little is known regarding the effects of human Wharton's jelly derived MSCs on HSC expansion and red blood cell (RBC) generation in vitro. This study aimed to investigate the effects of MSCs on HSC expansion and differentiation. HSCs were co-cultured with MSCs or with 10% MSCs-derived conditioned medium, with HSCs cultured under standard medium served as a control. Cell expansion rates, number of mononuclear cell post-expansion and number of enucleated cells post-differentiation were evaluated. HSCs showed superior proliferation in the presence of MSC with mean expansion rate of 3.5 × 108 ± 1.8 × 107 after day 7 compared to the conditioned medium and the control group (8.9 × 107 ± 1.1 × 108 and 7.0 × 107 ± 3.3 × 106 respectively, P < 0.001). Although no significant differences in RBC differentiation were observed between groups at passage IV, the number of enucleated cell was greater compared to earlier passages, indicating successful RBC differentiation. Cord blood-derived CD34+ HSCs can be greatly expanded by co-culturing with MSCs without affecting the RBC differentiation capability, suggesting the importance of direct MSC-HSCs contact in HSC expansion and RBC differentiation.

Genetic analysis of the M2/ANXA5 haplotype as recurrent pregnancy loss predisposition in the Malay population.

PURPOSE: The aim of this study was to evaluate a new predisposition factor, M2/ANXA5 (RPRGL3), in recurrent pregnancy loss (RPL) patients of Malay origin, since it was previously known that the prevalence of this condition is relatively high among the Malay population of Malaysia, where conventional hereditary thrombophilia factors have been generally ruled out. METHODS: A total of 232 women who had experienced ≥2 unexplained RPL and 141 available male partners were recruited, with 360 healthy Malay and 166 parous female controls. Prevalence of M2 carriage and RPL odds ratios were calculated in (a) control and patient groups; (b) clinically defined subgroups in categories of pregnancy loss, primary, secondary, and tertiary; and (c) timing of pregnancy loss in early, ≤15th gestation week and "late" fetal losses, and >15th gestation week subgroups. RESULTS: Both male and female subjects had similar M2/ANXA5 allele frequencies. The carrier rate of M2/ANXA5 for the general Malay population was 42.2 and 34.9% for parous controls. These carrier rates compared to Malay RPL subjects (52% M2 carriers) resulted in elevated odds ratios (95% confidence interval) of 1.53 (1.1 to 2.1) and 1.97 (1.3 to 3.1) accordingly for early fetal losses. Moreover, exceeding copy numbers of M2/ANXA5 alleles seemed to afflict a greater chance of RPL in couples, especially when both partners were M2 carriers. CONCLUSION: This study confirmed the proposed role of M2/ANXA5 as embryonic, genetically associated thrombophilia predisposition factor for early RPL among ethnic Malay of Malaysia.

Human non-small cell lung cancer expresses putative cancer stem cell markers and exhibits the transcriptomic profile of multipotent cells.

BACKGROUND: Despite significant advances in staging and therapies, lung cancer remains a major cause of cancer-related lethality due to its high incidence and recurrence. Clearly, a novel approach is required to develop new therapies to treat this devastating disease. Recent evidence indicates that tumours contain a small population of cells known as cancer stem cells (CSCs) that are responsible for tumour maintenance, spreading and resistant to chemotherapy. The genetic composition of CSCs so far is not fully understood, but manipulation of the specific genes that maintain their integrity would be beneficial for developing strategies to combat cancer. Therefore, the goal of this study isto identify the transcriptomic composition and biological functions of CSCs from non-small cell lung cancer (NSCLC). METHODS: We isolated putative lung CSCs from lung adenocarcinoma cells (A549 and H2170) and normal stem cells from normal bronchial epithelial cells (PHBEC) on the basis of positive expression of stem cell surface markers (CD166, CD44, and EpCAM) using fluorescence-activated cell sorting. The isolated cells were then characterised for their self-renewal characteristics, differentiation capabilities, expression of stem cell transcription factor and in vivo tumouregenicity. The transcriptomic profiles of putative lung CSCs then were obtained using microarray analysis. Significantly regulated genes (p < 0.05, fold change (FC) > 2.0) in putative CSCs were identified and further analysed for their biological functions using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). RESULTS: The putative lung CSCs phenotypes of CD166(+)/CD44(+) and CD166(+)/EpCAM(+) showed multipotent characteristics of stem cells, including the ability to differentiate into adipogenic and osteogenic cells, self-renewal, and expression of stem cell transcription factors such as Sox2 and Oct3/4. Moreover, the cells also shows the in vivo tumouregenicity characteristic when transplanted into nude mice. Microarray and bioinformatics data analyses revealed that the putative lung CSCs have molecular signatures of both normal and cancer stem cells and that the most prominent biological functions are associated with angiogenesis, migration, pro-apoptosis and anti-apoptosis, osteoblast differentiation, mesenchymal cell differentiation, and mesenchyme development. Additionally, self-renewal pathways such as the Wnt and hedgehog signalling pathways, cancer pathways, and extracellular matrix (ECM)-receptor interaction pathways are significantly associated with the putative lung CSCs. CONCLUSION: This study revealed that isolated lung CSCs exhibit the characteristics of multipotent stem cells and that their genetic composition might be valuable for future gene and stem cells therapy for lung cancer.

WITHDRAWN: Rh genotypes among Malaysian blood donors.

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The effects of virgin coconut oil (VCO) as supplementation on quality of life (QOL) among breast cancer patients.

BACKGROUND: Breast cancer is the most common cancer amongst Malaysian women. Both the disease and its treatment can disrupt the lives of the woman and adversely affect all aspects of life and thus can alter a woman's quality of life. The aim of this study was to examine the effect of virgin coconut oil (VCO) on the quality of life (QOL) of patients diagnosed with breast cancer. METHODS: This was a prospective study of breast cancer patients admitted into the Oncology Unit of Hospital Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia. The sample consisted of 60 patients with stage III and IV breast cancer allocated to either an intervention group (n = 30) or a control group (n = 30) using a simple random table. QOL was evaluated from the first cycle of chemotherapy to the sixth cycle, and data were collected using a validated Bahasa Malaysia version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC QLQ-C30) and its breast-specific module (QLQ-BR 23). RESULTS: The mean age of breast cancer patients was 50.2 (SD = 13.5) years. There were significant mean score differences for functioning and global QOL between groups (α < 0.01). The intervention group also had better scores for symptoms including fatigue, dyspnea, sleep difficulties, and loss of appetite compared to the control group. Although there are deteriorations for sexual enjoyment, the intervention group exhibited improvement in breast functioning and symptom scores for body image, sexual function, future perspective, breast symptoms, and systemic therapy side effects. CONCLUSION: VCO consumption during chemotherapy helped improve the functional status and global QOL of breast cancer patients. In addition, it reduced the symptoms related to side effects of chemotherapy.

Current perspectives on mesenchymal stem cells as a potential therapeutic strategy for non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant health challenge, characterized by its widespread prevalence, intricate natural progression and multifaceted pathogenesis. Although NAFLD initially presents as benign fat accumulation, it may progress to steatosis, non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. Mesenchymal stem cells (MSCs) are recognized for their intrinsic self-renewal, superior biocompatibility, and minimal immunogenicity, positioning them as a therapeutic innovation for liver diseases. Therefore, this review aims to elucidate the potential roles of MSCs in alleviating the progression of NAFLD by alteration of underlying molecular pathways, including glycolipid metabolism, inflammation, oxidative stress, endoplasmic reticulum stress, and fibrosis. The insights are expected to provide further understanding of the potential of MSCs in NAFLD therapeutics, and support the development of MSC-based therapy in the treatment of NAFLD.

Production and purification of polymerization-competent HIV-1 capsid protein p24 (CA) in NiCo21(DE3) Escherichia coli.

BACKGROUND: HIV genome is packaged and organized in a conical capsid, which is made up of ~1,500 copies of the viral capsid protein p24 (CA). Being a primary structural component and due to its critical roles in both late and early stages of the HIV replication cycle, CA has attracted increased interest as a drug discovery target in recent years. Drug discovery studies require large amounts of highly pure and biologically active protein. It is therefore desirable to establish a simple and reproducible process for efficient production of HIV-1 CA. RESULT: In this work, 6-His-tagged wild type CA from HIV-1 (NL4.3) was expressed in rare tRNA-supplemented NiCo21(DE3) Escherichia coli, and its production was studied in shake flask culture condition of expression. Influences of various key cultivation parameters were examined to identify optimal conditions for HIV-1 CA production. It was found that a culture temperature of 22°C and induction with 0.05 mM IPTG at the early stage of growth were ideal, leading to a maximum biomass yield when grown in Super broth supplemented with 1% glucose. With optimized culture conditions, a final biomass concentration of ~27.7 g L⁻¹ (based on optical density) was obtained in 12 hours post-induction, leading to a yield of about ~170 mg L⁻¹ HIV-1 CA. A two-step purification strategy (chitin beads + IMAC) was employed, which efficiently removed metal affinity resin-binding bacterial proteins that contaminate recombinant His-tagged protein preparation, and resulted in highly pure HIV-1 CA. The purified protein was capable of polymerization when tested in an in vitro polymerization assay. CONCLUSIONS: By using this optimized expression and purification procedure, milligram amounts of highly pure and polymerization-competent recombinant HIV-1 CA can be produced at the lab-scale and thus used for further biochemical studies.

Anti-angiogenic quassinoid-rich fraction from Eurycoma longifolia modulates endothelial cell function.

Targeting angiogenesis could be an excellent strategy to combat angiogenesis-dependent pathophysiological conditions such as cancer, rheumatoid arthritis, obesity, systemic lupus erythematosus, psoriasis, proliferative retinopathy and atherosclerosis. Recently a number of clinical investigations are being undertaken to assess the potential therapeutic application of various anti-angiogenic agents. Many of these angiogenesis inhibitors are directed against the functions of endothelial cells, which are considered as the building blocks of blood vessels. Similarly, roots of a traditional medicinal plant, Eurycoma longifolia, can be used as an alternative treatment to prevent and treat the angiogenesis-related diseases. In the present study, antiangiogenic potential of partially purified quassinoid-rich fraction (TAF273) of E. longifolia root extract was evaluated using ex vivo and in vivo angiogenesis models and the anti-angiogenic efficacy of TAF273 was investigated in human umbilical vein endothelial cells (HUVEC). TAF273 caused significant suppression in sprouting of microvessels in rat aorta with IC50 11.5µg/ml. TAF273 (50µg/ml) showed remarkable inhibition (63.13%) of neovascularization in chorioallantoic membrane of chick embryo. Tumor histology also revealed marked reduction in extent of vascularization. In vitro, TAF273 significantly inhibited the major angiogenesis steps such as proliferation, migration and differentiation of HUVECs. Phytochemical analysis revealed high content of quassinoids in TAF273. Specially, HPLC characterization showed that TAF273 is enriched with eurycomanone, 13α(21)-epoxyeurycomanone and eurycomanol. These results demonstrated that the antiangiogenic activity of TAF273 may be due to its inhibitory effect on endothelial cell proliferation, differentiation and migration which could be attributed to the high content of quassinoids in E. longifolia.

X-linked chronic granulomatous disease in a male child with an X-CGD carrier, Klinefelter brother.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency (PID) caused by a dysfunctional respiratory burst enzyme NADPH-oxidase. The concurrence of Klinefelter's Syndrome (KS) and CGD would be extremely rare. OBJECTIVE: We describe the study of a family where the youngest male child had X-linked CGD (X-CGD) while his older brother was both an X-CGD carrier and a Klinefelter. METHODS: Flow cytometry was used to study respiratory burst and gp91-phox expression, while genetic investigation was done by RT-PCR, PCR and X-chromosome short tandem repeat (X-STR) analysis. RESULTS: The Dihydrorhodamine (DHR) assay showed the patient's neutrophils failed to produce a respiratory burst, while both the mother and an older brother showed a bimodal response. gp91-phox expression was absent in the patient's neutrophils, and bimodal in the mother's and brother's neutrophils. The patient's cDNA showed a C>T change at nucleotide 676 of the CYBB gene. The same change was seen in the patient's gDNA, while the brother and mother were heterozygous, with C and T, in this position. The c.676C>T is a nonsense mutation that leads to premature termination of the gp91-phox protein. The brother karyotyped as 47, XXY and X chromosome analysis showed that he had inherited both his mother's X chromosomes. CONCLUSIONS: This study showed that the patient had gp91-phox deficient CGD while his older brother was a CGD carrier and a Klinefelter, who had inherited both his mother's X chromosomes. This is the first report of such a concurrence in an individual, and argues for family members to be included in PID studies.

Cytogenetics analysis as the central point of genetic testing in acute myeloid leukemia (AML): a laboratory perspective for clinical applications.

Chromosomal abnormalities in acute myeloid leukemia (AML) have significantly contributed to scientific understanding of its molecular pathogenesis, which has aided in the development of therapeutic strategies and enhanced management of AML patients. The diagnosis, prognosis and treatment of AML have also rapidly transformed in recent years, improving initial response to treatment, remission rates, risk stratification and overall survival. Hundreds of rare chromosomal abnormalities in AML have been discovered thus far using chromosomal analysis and next-generation sequencing. As a result, the World Health Organization (WHO) has categorized AML into subgroups based on genetic, genomic and molecular characteristics, to complement the existing French-American classification which is solely based on morphology. In this review, we aim to highlight the most clinically relevant chromosomal aberrations in AML together with the technologies employed to detect these aberrations in laboratory settings.

RUNX1/ETO regulates reactive oxygen species (ROS) levels in t(8,21) acute myeloid leukaemia via FLT3 and RAC1.

Reactive oxygen species (ROS) homeostasis is crucial for leukaemogenesisand deregulation would hamper leukaemic progression. Although the regulatory effects of RUNX1/ETO has been extensively studied, its underlying molecular mechanims in ROS production in t(8,21) AML is yet to be fully elucidated. Here, we report that RUNX1/ETO could directly control FLT3 by occupying several DNA elements on FLT3 locus. The possible hijacking mechanism by RUNX1/ETO over FLT3 mediated ROS modulation in AML t(8;21) was made apparent when suppression of RUNX1/ETO led to decrement in ROS levels and the direct oxidative marker FOXO3 but not in FLT3 and RAC1 suppressed t(8,21) AML cell line Furthermore, nuclear import of RUNX1/ETO was aberrated following RUNX1/ETO and RAC1 suppression suggesting association in ROS control. A different picture was depicted in non t(8;21) cells where suppression of RAC1 and FLT3 led to decreased levels of FOXO3a and ROS. Results alltogether indicate a possible dysregulation of ROS levels by RUNX1/ETO in t(8,21) AML.

Elucidating miRNA Function in Cancer Biology via the Molecular Genetics' Toolbox.

Micro-RNA (miRNAs) are short non-coding RNAs of about 18-20 nucleotides in length and are implicated in many cellular processes including proliferation, development, differentiation, apoptosis and cell signaling. Furthermore, it is well known that miRNA expression is frequently dysregulated in many cancers. Therefore, this review will highlight the various mechanisms by which microRNAs are dysregulated in cancer. Further highlights include the abundance of molecular genetics tools that are currently available to study miRNA function as well as their advantages and disadvantages with a special focus on various CRISPR/Cas systems This review provides general workflows and some practical considerations when studying miRNA function thus enabling researchers to make informed decisions in regards to the appropriate molecular genetics tool to be utilized for their experiments.

Analysis of Common Beta-Thalassemia (ß-Thalassemia) Mutations in East Java, Indonesia.

Background: The frequency of the beta-thalassemia (ß-thalassemia) gene in Indonesia ranges from 3 to 10%. However, in the East Java province, there is still limited information on the prevalence of ß-thalassemia mutations in clinically diagnosed beta-thalassemia patients of East Java. Therefore, this study aimed to characterize ß-thalassemia mutations in selected patients in the East Java province of Indonesia. Methods: This is an analytical observational study. Diagnosis of ß-thalassemia was based on clinical presentation, complete blood count (CBC), and hemoglobin (Hb) electrophoresis. Blood specimens taken from each patient in three ethylenediaminetetraacetic acid (EDTA) tubes were analyzed for CBC and Hb electrophoresis and processed for DNA extraction and subsequent polymerase chain reaction (PCR). Detection of mutations in Hemoglobin Subunit Beta (HBB) gene exons 1-3 of the ß-thalassemia gene as the common mutation in Indonesia was done using PCR followed by Sanger sequencing. Results: In total, 33 (n = 33) participants were involved in this study with ages ranging from 5 to 17 years comprising 19 women and 14 men. Their ethnic origins were Javanese (n = 30) and Chinese (n = 3). CBC results showed that mean ± standard deviation (SD) for Hb, red blood cell (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red cell distribution width (RDW)-CV were 81.2 ± 7.0 g/L; 3.40 ± 0.39 × 109/L; 71.05 ± 5.72 fL; 24.12 ± 2.45 pg; 33.91 ± 1.47 g/dl; 24.38 ± 6.02%, respectively. Hb electrophoresis revealed that 5 out of 33 participants had beta-thalassemia and 28 out of 33 participants had hemoglobinopathy (Hb) E/beta-thalassemia. Results of Sanger sequencing showed the following genotype variations in the samples: 12 (36.4%) with ß CD26 /ß IVS-I-5; 6 (18.2%) with ß CD26 /ß CD35; 3 (9.1%) with ß CD26 /ß IVS-I-2; 2 (6.1%) with ß CD27/28 /ß CD40; 2 (6.1%) with ß IVS-I-1 /ß CAP+1; and ß CD26 /ß IVS-I-1; ß IVS-I-5 /ß CAP+1; ß IVS-I-5 /ß CD35; ß CD26 /ß CD37; ß CD26 /ß CD15; ß CD26 /ß CD40; and ß IVS-I-5 /ß CD19 in 1 (3%) sample, respectively, and 1 (3%) had no abnormality detected in sequencing even though electrophoresis showed abnormality in the migration pattern. The ß CD26 /ß IVS-I-5 mutation was found in samples that were noted to have Hb E/beta-thalassemia on Hb electrophoresis. Conclusion: The underlying genetic variations are heterogeneous in thalassemia patients in East Java, where 12 variants were found. The most common variant was ß CD26 /ß IVS-I-5, which all accounted for Hb E/beta-thalassemia on Hb electrophoresis. Furthermore, 28 out of 33 participants had hemoglobinopathy (Hb) E/beta-thalassemia.

Central resources of variant discovery and annotation and its role in precision medicine.

Rapid technological advancement in high-throughput genomics, microarray, and deep sequencing technologies has accelerated the possibility of more complex precision medicine research using large amounts of heterogeneous health-related data from patients, including genomic variants. Genomic variants can be identified and annotated based on the reference human genome either within the sequence as a whole or in a putative functional genomic element. The American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) mutually created standards and guidelines for the appraisal of proof to expand consistency and straightforwardness in clinical variation interpretations. Various efforts toward precision medicine have been facilitated by many national and international public databases that classify and annotate genomic variation. In the present study, several resources are highlighted with recognition and data spreading of clinically important genetic variations.

Markers of Renal Complications in Beta Thalassemia Patients with Iron Overload Receiving Chelation Agent Therapy: A Systematic Review.

Objective: The emerging renal complications in beta-thalassemia patients have raised the global exchange of views. Despite better survival due to blood transfusion and iron chelation therapy, the previously unrecognized renal complication remain a burden of disease affecting this population -the primary concern on how iron overload and chelation therapy correlated with renal impairment is still controversial. Early detection and diagnosis is crucial in preventing further kidney damage. Therefore, a systematic review was performed to identify markers of kidney complications in beta thalassemia patients with iron overload receiving chelation therapy. Methods: Searches of PubMed, Scopus, Science Direct, and Web of Science were conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to identify studies of literature reporting renal outcome in ß-TM patients with iron overload and receiving chelation therapy. The eligible 17 studies were obtained. Results: uNGAL/NGAL, uNAG/NAG, uKIM-1 are markers that can be used as predictor of renal tubular damage in early renal complications, while Cystatin C and uß2MG showed further damage at the glomerular level. Discussion and Conclusion: The renal complication in beta-thalassemia patients with iron overload receiving chelating agent therapy may progress to kidney disease. Early detection using accurate biological markers is a substantial issue that deserves further evaluation to determine prevention and management.

Mechanism of Human Telomerase Reverse Transcriptase (hTERT) Regulation and Clinical Impacts in Leukemia.

The proliferative capacity and continuous survival of cells are highly dependent on telomerase expression and the maintenance of telomere length. For this reason, elevated expression of telomerase has been identified in virtually all cancers, including leukemias; however, it should be noted that expression of telomerase is sometimes observed later in malignant development. This time point of activation is highly dependent on the type of leukemia and its causative factors. Many recent studies in this field have contributed to the elucidation of the mechanisms by which the various forms of leukemias increase telomerase activity. These include the dysregulation of telomerase reverse transcriptase (TERT) at various levels which include transcriptional, post-transcriptional, and post-translational stages. The pathways and biological molecules involved in these processes are also being deciphered with the advent of enabling technologies such as next-generation sequencing (NGS), ribonucleic acid sequencing (RNA-Seq), liquid chromatography-mass spectrometry (LCMS/MS), and many others. It has also been established that TERT possess diagnostic value as most adult cells do not express high levels of telomerase. Indeed, studies have shown that prognosis is not favorable in patients who have leukemias expressing high levels of telomerase. Recent research has indicated that targeting of this gene is able to control the survival of malignant cells and therefore offers a potential treatment for TERT-dependent leukemias. Here we review the mechanisms of hTERT regulation and deliberate their association in malignant states of leukemic cells. Further, we also cover the clinical implications of this gene including its use in diagnostic, prognostic, and therapeutic discoveries.

Utilization of CRISPR-Mediated Tools for Studying Functional Genomics in Hematological Malignancies: An Overview on the Current Perspectives, Challenges, and Clinical Implications.

Hematological malignancies (HM) are a group of neoplastic diseases that are usually heterogenous in nature due to the complex underlying genetic aberrations in which collaborating mutations enable cells to evade checkpoints that normally safeguard it against DNA damage and other disruptions of healthy cell growth. Research regarding chromosomal structural rearrangements and alterations, gene mutations, and functionality are currently being carried out to understand the genomics of these abnormalities. It is also becoming more evident that cross talk between the functional changes in transcription and proteins gives the characteristics of the disease although specific mutations may induce unique phenotypes. Functional genomics is vital in this aspect as it measures the complete genetic change in cancerous cells and seeks to integrate the dynamic changes in these networks to elucidate various cancer phenotypes. The advent of CRISPR technology has indeed provided a superfluity of benefits to mankind, as this versatile technology enables DNA editing in the genome. The CRISPR-Cas9 system is a precise genome editing tool, and it has revolutionized methodologies in the field of hematology. Currently, there are various CRISPR systems that are used to perform robust site-specific gene editing to study HM. Furthermore, experimental approaches that are based on CRISPR technology have created promising tools for developing effective hematological therapeutics. Therefore, this review will focus on diverse applications of CRISPR-based gene-editing tools in HM and its potential future trajectory. Collectively, this review will demonstrate the key roles of different CRISPR systems that are being used in HM, and the literature will be a representation of a critical step toward further understanding the biology of HM and the development of potential therapeutic approaches.

Footprints of microRNAs in Cancer Biology.

MicroRNAs (miRNAs) are short non-coding RNAs involved in post-transcriptional gene regulation. Over the past years, various studies have demonstrated the role of aberrant miRNA expression in the onset of cancer. The mechanisms by which miRNA exerts its cancer-promoting or inhibitory effects are apparent through the various cancer hallmarks, which include selective proliferative advantage, altered stress response, vascularization, invasion and metastasis, metabolic rewiring, the tumor microenvironment and immune modulation; therefore, this review aims to highlight the association between miRNAs and the various cancer hallmarks by dissecting the mechanisms of miRNA regulation in each hallmark separately. It is hoped that the information presented herein will provide further insights regarding the role of cancer and serve as a guideline to evaluate the potential of microRNAs to be utilized as biomarkers and therapeutic targets on a larger scale in cancer research.