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Background: Chronic myeloid leukemia (CML) results from chromosomal translocation t(9;22) leading to the formation of the BCR-ABL fusion oncogene. CML has three stages: the chronic phase (CP), the accelerated phase (AP), and the blast crisis (BC). Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of CML. TKIs work well in CP-CML, and these patients have a survival rate similar to the normal population, but TKIs are less effective in advanced-phase CML. Even with current advances in treatment, BC-CML patients have an average overall survival of less than a year. Early recognition of CML patients at risk of disease progression can help in timely interventions with appropriate TKIs or other therapeutic modalities. Although some markers of disease progression like BCR-ABL kinase domain, ASXL1, and GATA2 mutations are available, no universal and exclusively specific molecular biomarkers exist to early diagnose CML patients at risk of CML progression for timely therapeutic interventions to delay or minimize blast crisis transformation in CML. A recent study found that all BC-CML patients harbored the FANCD2 (c.2022-5C>T) mutation. Therefore, the current study was designed to detect this FANCD2 mutant in AP-CML (early progression phase) and to clinically validate its potential as a novel molecular biomarker of early CML progression from CP to AP. Methods: Our study comprised 123 CP-CML (control group) and 60 AP-CML patients (experimental group) from 2 oncology centers, from January 2020 to July 2023. Mean hemoglobin level, WBC count, platelet count, treatment type, hepatomegaly, splenomegaly, and survival status of AP-CML patients were significantly different from those of CP-CML patients. However, as these clinical parameters cannot help in the early detection of patients at risk of CML progression, there was a need for a clinically validated biomarker of AP-CML. DNA was extracted from the patients' blood samples, and the FANCD2 gene was sequenced using an Illumina NextSeq500 next-generation sequencer (NGS). Results: The NGS analysis revealed a unique splice-site mutation in the FANCD2 gene (c.2022-5C>T). This mutation was detected in the majority (98.3%) of AP-CML patients but in none of the CP-CML patients or healthy control sequences from genomic databases. The mutation was confirmed by Sanger sequencing. FANCD2 is a member of the Fanconi anemia pathway genes involved in DNA repair and genomic stability, and aberrations of this gene are associated with many cancers. Conclusions: In conclusion, our study shows that the somatic FANCD2 (c.2022-5C>T) mutation is a new molecular biomarker for early CML progression. We recommend further clinical validation of this biomarker in prospective clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: Idiopathic osteosclerosis (IO) refers to dense bone islands seen in the jaw bones. They mimic a variety of bony lesions such as inflammatory, benign Odontogenic tumors, and intermediate fibro-osseous lesions. Accurate diagnosis of these lesions will eliminate the possibility of unnecessary intervention. Aim: To determine the characteristics and radiographic appearance of IO in the adult population of Saudi Arabia. Material and Methods: Digital panoramic radiographs (DPRs) of 2,854 subjects were analyzed for the presence of IO in the jaws. Descriptive characteristics including number, shape, localization, and relationship with dentition were recorded. The frequency was presented in numbers and percentages. The inferential analysis involved a chi-square test. Results: A total of 89 IO were detected in 86 OPGs. Solitary IO was identified in 83 OPGs with the presence of two IO's each in the remaining three radiographs. The overall patient-wise prevalence was 3.11%. No gender predilection was found in the studied population. However, a significant (P = 0.000) definite tendency for occurrence in the mandible (96.6%) was recorded. A significant (P = 0.000) preference of IO was seen with regard to the location with predominance observed for molar (55.06%). For the most part, IO was found to be significantly higher in the apical region (42.69%) of teeth compared to other contemporaries. Significant variations were also observed in shape and size with the majority of lesions observed to be irregular (95.5%) and 1-2cm in size (37.07%). Conclusion: Although, IO occurs infrequently in jaw bones periapical location being the favored, warrants clear differentiation of IO from inflammatory lesions. [ABSTRACT FROM AUTHOR]

Background: Various methods are used for gender identification in anthropologic and forensic investigations. The canine tooth are widely used for gender determination because of its sexual dimorphism and durability in oral cavity. Mandibular canine index is one of the most reliable and valid predictor for gender identification. Aim: To assess the reliability of Mandibular Canine Index in gender determination in North Saudi Sakaka populations. Settings and Design: This was an experimental study involving the preparation of plaster cast models on 100 individuals residing in North Saudi Sakaka populations. Out of these 55 were males and 45 were females. Both sexes were in the age group of 20- 40 years old. Study casts were prepared for all individuals and the measurements of mandibular canine teeth were taken. The Mandibular canine index was calculated using standardized equation. In addition, the percentage of sexual dimorphism was calculated. Independent sample t test was used. P value < 0.05 was considered statistically significant. Results: There was a significant difference (p value < 0.05) observed between intercanine distance, right and left canine width and right and left mandibular canine index between males and females. Sexual dimorphism was more on left permanent mandibular canine teeth than right permanent mandibular canine teeth. The overall percentage of accuracy observed was 85.5 %. Conclusions: Study findings revealed that mandibular canine index can be used as a reliable predictor for gender determination in Sakaka population and can form the basis of anthropologic and forensic investigations. [ABSTRACT FROM AUTHOR]

Tyrosine Kinase Inhibitors (TKIs) have significantly improved the clinical outcome of BCR-ABL+ Chronic Phase-Chronic Myeloid Leukemia (CP-CML). Nonetheless, approximately one-third of the CP-CML patient's progress to advanced phases of CML (accelerated and blast phase). Impaired DNA repair including mutations in Fanconi anemia (FA) pathway genes are responsible for progression of many cancers. Nevertheless, FA-pathways genes have never been reported in myeloid cancers. Hence, this study was aimed to discover DNA repair genes associated with CML progression. AP-CML patients were subjected to whole exome sequencing along with appropriate controls. A novel splice site FANCD2 mutation was detected. FANCD2 is a well-known FA-pathway gene with established role in DNA repair. This is first report of FA-pathway DNA repair genes in myeloid cancers that can serve as a novel marker of CML progression to clinically intervene CML progression. Further studies are needed to establish the functional role of FANCD2 in CML progression that can provide novel insights into CML pathogenesis. This study also indicates that a combination TKIs and Poly (ADP-ribose) polymerase (PARP) inhibitors like Olaparib (FDA approved anti-cancer drug for FA-pathway gene mutations) could improve the clinical outcome CML patients in accelerated and blast-crisis phases of the disease.