Lack of FLT3-ITD in Tunisian childhood acute lymphoblastic leukemia

Background: The fms-like tyrosine kinase 3 (FLT3) gene belong to the class III receptor tyrosine kinases witch is predominantly expressed on hematopoietic progenitor cells, and plays an important role in haematopoiesis. Targeting the FMS-like tyrosine kinase receptor-3 (FLT3) in acute leukemia is mainly important. Therefore, activating mutations in FLT3, primarily the FLT3-internal tandem duplication (FLT3-ITD), was used as a prognostic marker especially in myeloid leukemia; however, in ALL, the prognostic relevance of FLT3 mutations is less clear. Objectives: This study was conducted to evaluate the frequency of FLT3-ITD mutation in Tunisian childhood acute lymphoblastic leukemia, and to correlate this mutation with prognostic parameters. Methods: Genomic DNA was extracted from EDTA-anticoagulant blood samples from a total of 25 children suffering from acute lymphoblastic leukemia (ALL). After DNA extraction, the polymerase chain reaction using specific primers was conducted to screen the FLT3-ITD. Results: In acute lymphoblastic leukemia (ALL), 9 cases with LAL-B were detected and the median age is 13 years. Chromosome abnormalities were detected in 5 with ALL and are correlated with worse prognosis (very high risk and relapse). At molecular lever, never FLT3-ITD was detected. Conclusions: Our findings suggest that FLT3 mutations are not common in Tunisian childhood ALL and thus do not affect clinical outcome. Keywords: Fms-like tyrosine kinase 3; internal tandem duplication; acute lymphoblastic leukemia

Animal models of osteoarthritis: Characterization of a model induced by Mono-Iodo-Acetate injected in rabbits

Knee Osteoarthritis is a considerable public health concern, both in terms of life quality and treatment financial impacts. To investigate this disease, animal models are deemed a promising alternative. In fact, although a perfect model is generally farfetched, the creation of models that simulate human disease as accurately as possible remains an important research stake. This study aims to highlight the usefulness of the model induced by injected Mono-Iodo-Acetate and to standardize it for the rabbit species. Osteoarthritis was induced by an infra-patellar injection of 0.2 ml of an MIA solution in the left knee of 24 female New Zealand rabbits. The right knee served as a control by receiving an injection of physiological serum. The rabbits were divided into 4 groups of 6 individuals each according to the dose of MIA received per knee. All rabbits were euthanized 30 days after the injection. After sacrifice, the knees were carefully dissected and macroscopic and microscopic scores of cartilage, meniscal and synovial lesions were attributed to each group. Our study followed the laboratory animal care and management guideline published in 2017 by the Canadian Council of Animal Care. The control knees of all rabbits showed no macroscopic or microscopic lesions. The macroscopic lesions: osteophytes, meniscal lesions, fibrillation and erosion of the cartilage and microscopic lesions: disorganization of the chondrocytes, decrease in proteo- glycans and synovial inflammation clinically diagnosed in human pathology were all detected and were similarly reproducible among the knees of the same group. Through this work, we highlighted the merits of the arthritis model induced by MIA, namely its simulation of several aspects of human pathology. Further advantages are low cost, speed, reproducibility. This model notably avoids delicate and risky surgical operations