Assessment of molecular response to tyrosine kinase inhibitors in Tunisian Patients with Chronic Myeloid Leukemia.

AIM: This study was carried out to assess the minimal residual disease in Tunisian patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors in routine clinical practice, to recognize potentially eligible carrier for treatment discontinuation, based on a molecular response (MR). PATIENTS AND METHODS: A retrospective study was carried out in the Hospital University of Sfax, south of Tunisia from January 2016 to October 2020, including all CML patients in the chronic phase at diagnosis, treated with TKI (tyrosine kinase inhibitors) for a minimum duration of 6 months. Quantitative assessment of the BCR-ABL transcript was performed using the Cepheid Xpert BCR-ABL ultra-assay. Molecular response and outcome were evaluated, according to the European Leukemia Net guidelines. RESULTS: A total of 162 CML patients were carried out. The median age was 50 years, the sex ratio M/F was 1.62. The rate of cumulative EMR; MMR and DMR was 80.8%; 73.8% and 55.9% respectively. According to the ELN criteria, 141 CML patients were evaluable. Optimal, suboptimal response and failure were noted in 81 (57.4%), 33(23.4%), and 27(19.1%) patients, respectively. Overall survival (OS) and progression-free survival (PFS) were 96.3% and 85%. Risk factors for an event (death/progression) were lack of EMR, MMR, and DMR (P < 0.05). Among 149 patients with sustained DMR; 14 (8.6%) CML patients have discontinued TKI therapy. CONCLUSION: Despite the limit of our study (duration and size), the available real-life molecular responses with TKI therapy should be considered to identify potentially CML patients eligible for discontinuation of TKI therapy.

MTHFR 677T-1298C haplotype in acute lymphoblastic leukemia: Impact on methotrexate therapy.

INTRODUCTION: Functional variants of the Methylenetetrahydrofolate reductase (MTHFR) gene, the C677T and A1298C, have largely investigated in pharmacogenomics of Methotrexate (MTX) in acute lymphoblastic leukemia (ALL), yet the conclusions are inconsistent. In addition; most of these studies do not analyze haplotypes. Here, we investigate the MTHFR 677/1298 genotypes and the 677-1298 haplotype and characterize the MTX response in Northern African ALL patients. METHODS: Genomic DNA was extracted from whole venous from a total of 28 patients with ALL. Genotyping were carried out with restriction fragment length polymorphism (RFLP). A toxicity score (TS) is calculated for each patient and correlate to the haplotype. RESULTS: The allelic frequency of MTHFR 677T-1298C haplotype was 10.7% in ALL patients. According to the toxicity's score (TS) there was no significant differences between haplotype groups (p = 0.79): TS was higher with wild type of MTHFR (TS = 3.43; SEM ± 0.85) followed by combined genotype (677T-1298C) (TS = 2.67; SEM ± 0.88) and isolated variant (C677T or A1298C) (TS = 2.64; SEM ± 0.92). CONCLUSION: Despite the limitation of this study; our results suggest that the MTHFR 677T-1298C haplotype is common in ALL and may be a promising HD-MTX chemotherapy-related adverse effects biomarker.

Involvement of MTHFR rs1801133 in the Susceptibility of Acute Lymphoblastic Leukemia: A Preliminary Study.

BACKGROUND: Acute lymphoblastic leukemia (ALL), a common blood cancer, is characterized by the interaction between genetic and environmental factors. Several variants of the Methylenetetrahydrofolate reductase (MTHFR), mainly the C677T (rs1801133), may affect susceptibility to ALL. AIM OF THE STUDY: The authors conducted this case-control study to evaluate the relationship between this variant of the MTHFR gene and the risk of ALL. MATERIALS AND METHODS: Forty-one patients with ALL and 35 non-ALL controls recruited in this study were genotyped utilizing polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The MTHFR 677CT genotype was significantly more frequently found in patients with ALL having a 2-fold increase in risk (P <0.01). CONCLUSION: Our results suggest that rs1801133 of MTHFR is a predictive risk marker to ALL in Tunisian ALL.

Co-existence of BCR-ABL and JAK2V617F mutation in resistant chronic myeloid leukemia in the imatinib era: Is there a correlation?

INTRODUCTION: Diagnoses of myeloproliferative disorder is based on molecular marker. Chronic Myeloid Leukemia and Myeloproliferative neoplasms were considered mutually exclusive and co-existence of BCR/ABL1 and JAK2 mutation is a rare phenomenon. CASE REPORT: Here, we present two cases of co-existence of BCR-ABL and JAK2V617F positivity. We characterize the course of the disease, mainly the minimal residual disease.Management and outcome: The two cases was initially managed as Chronic Myeloid Leukemia and treated by TKI inhibitors. The first one was diagnosed in 2010. He started the first line of TKI, and then switched to second line without obtaining a major molecular response. Hence he was tested for JAK2V617F mutation and positivity was diagnosed. The second patient showed Chronic Myeloid Leukemia phenotype with coexistence of BCR/ABL1 and JAK2 mutation at diagnosis. Molecular monitoring reveals a high BCR-ABL1 transcript level (20%) at the last follow-up (12 months). DISCUSSION: Ours results highlight that JAK2V617F/BCR-ABL double positivity may be a potential marker of resistance in Chronic Myeloid Leukemia and clonal molecular analysis is mandatory to elucidate the mechanism. Moreover, the combination of JAK and TKI inhibitors might be effective and potentially be guided by molecular monitoring of minimal residual disease.

Involvement of C677T MTHFR variant but not A1298C in methotrexate-induced toxicity in acute lymphoblastic leukemia.

BACKGROUND: Methotrexate (MTX) is a key drug in acute lymphoblastic leukemia (ALL) treatment; it inhibits DNA replication by blocking the conversion of 5, 10 Methylenetetrahydrofolate to 5-methylene tetrahydrofolate by methylenetetrahydrofolate reductase (MTHFR). Variants of the Methylenetetrahydrofolate reductase (MTHFR) and MTX related toxicities were largely investigated in several populations, nevertheless, the results are conflicting. OBJECTIVE: This study aimed to assess the prevalence of MTHFR SNVs: C677>T and A1298>C in Tunisian patients with ALL and the relation to the frequency of drug-induced complications. METHODS: 28 ALL patients were included in the study. They were treated according to EORTOC, in which a high dose of MTX (HDMTX) was prescribed. A toxicity score (ST) is calculated for each patient, summing the grades of toxicities. Genotyping of MTHFR variants was done with a PCR-based restriction fragment length polymorphism assay. RESULTS: The toxicity's score (TS) was higher with C677T variant compared to wild genotype (C677C) (TS = 4; IC95% [-2.65-13.32] versus TS = 2.5; IC95% [1.65-4.55], respectively; p = 0.2); but lower with the A1298C mutation compared to those with the wild genotype (A1298A) (TS = 2.5; IC95% [0.48-4.77], versus TS =3; IC95% [1.9-5.69], p = 0.4). HDMTX-related toxicity is associated with the 677CT genotype in ALL patients (RR = 1.41, p = 0.2); not for the A1298C [OR = 0.46, [0.08-2.61], p = 0.18]. CONCLUSION: Our preliminary findings highlight the impact of the C677T variant of MTHFR, but not the A1289C; in HD-MTX chemotherapy-related adverse effects in younger Tunisian ALL.

Assessment of the relationship between methylenetetrahydrofolate reductase polymorphism and acute lymphoblastic leukemia: Evidence from an updated meta-analysis.

OBJECTIVE: The methylenetetrahydrofolate reductase gene C677T polymorphism is closely related to the acute lymphoblastic leukemia. Several case-control studies have investigated this association; however, no conclusions could be drawn. A comprehensive updated meta-analysis is established to explain these contradictions and clarify the overall impact of this variant on the susceptibility to acute lymphoblastic leukemia. METHODS: Electronic searches were conducted to select published studies prior to June 2018. Pooled odds ratios and stratification analysis were performed under different genetic comparison models, age, and ethnicity. RESULTS: Totally, 66 case-control studies including 9619 acute lymphoblastic leukemia cases and 17,396 controls were selected. Our analyses showed that methylenetetrahydrofolate reductase C677T polymorphism was protective mainly in Asian and European countries, under all genetic models and regardless of age, but leukemogenic in mixed population. CONCLUSION: Thus, C677T polymorphism may be a promising acute lymphoblastic leukemia biomarker, but they should be interpreted with caution considering other factors such as folic acid intake, gene-gene and gene-environment interactions.

Comprehensive analysis of Methylenetetrahydrofolate reductase C677T in younger acute lymphoblastic leukemia patients: A single-center experience.

CONTEXT: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms, mainly the C677T, have been implicated as risk factors for several cancers as the acute lymphoblastic leukemia (ALL). In addition, a potential effect of such variant on the efficacy of methotrexate (MTX) has been reported. OBJECTIVE: In this study, we evaluated the impact of the C677T variant of MTHFR on MTX-related toxicity in ALL patients from Tunisia; to provide new insights for a personalized therapy based on the human genotype. MATERIALS AND METHODS: Genotyping was carried out with restriction fragment length polymorphism (RFLP) on blood samples from a total of 35 younger patients; suffering from ALL. RESULTS: In the ALL patients, the MTHFR 677CT genotype confers a greater risk of toxicity with 1.3 times as relative risk mainly the hepatic toxicity when compared with MTHFR 677CC. CONCLUSION: Our findings suggest that C677T polymorphism of MTHFR seems to be a good marker for MTX-related toxicity in ALL.

A duplex polymerase chain reaction-restriction fragment length polymorphism for rapid screening of methylenetetrahydrofolate reductase gene variants: Genotyping in acute leukemia.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR; NM_005957.4) is the key enzyme for folate metabolism which plays in DNA biosynthesis and the epigenetic process of DNA methylation. MTHFR gene polymorphisms, the c. 677C>T and c. 1298A>C have been implicated as risk factors for several types of cancers as the acute leukemia. AIM: We have optimized a duplex polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP) for the simultaneous detection of both variants in acute leukemia patients, from Tunisia. METHODS: Genomic DNA was extracted from EDTA-anticoagulant blood samples from a total of 50 patients suffering from acute leukemia (AL). After DNA extraction, the polymerase chain reaction using specific primers, designed using Primer 3 Software. Restriction Fragment Length Polymorphism (RFLP) was performed in two separate tubes followed by agarose gel electrophoresis. CONCLUSION: This new method has proved to be a rapid, simple, and reliable method that should facilitate high throughput genotyping of MTHFR polymorphisms in acute leukemia.

Impact of CYP1A1 variants on the risk of acute lymphoblastic leukemia: evidence from an updated meta-analysis.

OBJECTIVE: Our study aimed to investigate the association between cytochrome P450 1A1 (CYP1A1) polymorphisms (T3801C and A2455G) and acute lymphoblastic leukemia (ALL) risk, considering genetic models and ethnicity. MATERIALS AND METHODS: PubMed, Embase, Web of Knowledge, Scopus, and the Cochrane electronic databases were searched using combinations of keywords related to CYP1A1 polymorphisms and the risk of ALL. Studies retrieved from the database searches underwent screening based on strict inclusion and exclusion criteria. RESULTS: In total, 2822 cases and 4252 controls, as well as 1636 cases and 2674 controls of the C3801T and A2455G variants of CYP1A1, respectively, were included in this meta-analysis. The T3801C polymorphism of CYP1A1 significantly increases the risk of ALL, particularly those observed in Asian and Hispanic populations, independent of age. Similarly, the A2455G polymorphism of CYP1A1 plays a significant role in the susceptibility to ALL in all genetic models, except the heterozygous form. This association was observed mainly in mixed populations and in both children and adults (except in the heterozygous model). CONCLUSION: Our comprehensive analysis indicates that the T3801 and A2455G polymorphisms of CYP1A1 may increase the risk of ALL depending on ethnicity. Therefore, both variants should be considered promising biomarkers for ALL risk. Further large-scale investigations are necessary to assess other factors, such as gene-gene or gene-environment interactions.

Exploring the role of vitamin D-VDR pathway in pemphigus foliaceous: a novel perspective on disease pathogenesis.

Several auto-immune diseases have been linked to vitamin D deficiency as a contributing environmental factor. Its pleiotropic effects on the immune system, especially its essential role in maintaining immune tolerance, make the vitamin D pathway of great interest. In this study, we focused on Pemphigus foliaceous (PF) in Tunisian population. we aimed to quantify the Serum 25[OH]D levels using chemiluminescence assay and to analyze the differential expression of the VDR, CYP27B1 and CYP24A1 genes in the circulating blood cells and lesional skin tissue of PF patients using Q-PCR. A genetic explanation was then sought to explore any direct relationship between tag polymorphisms and the inherited features of PF. Results confirmed a vitamin D hypovitaminosis in Tunisian PF patients. Interestingly, a differential gene expression correlated to the disease stratification was noted. Indeed, at the systemic level, an upregulation of VDR and CYP27B1 genes was observed in healthy controls compared to PF patients. Notably, in lesional skin tissue, the clinical and serological remission phase was correlated with high transcriptional levels of the VDR gene and conversely a drop in expression of the CYP24A1 gene. Genetic analysis indicated the involvement of the most appealing polymorphisms, rs2228570 and poly (A) microsatellite, in PF etiopathogenesis. Indeed, CAC13 haplotype was associated with a higher risk of PF development. Our findings suggest that alterations in the vitamin D-VDR pathway may influence PF physiopathology, making this pathway a potential target for pharmacological modulation, especially for cortico-resistant PF patients.

Unraveling the role of the vitamin D-VDR pathway in pemphigus vulgaris from Tunisian patients.

Vitamin D dysregulation has been recognized as a factor that may cause or aggravate autoimmunity. Vitamin D deficiency was found to be common in pemphigus vulgaris (PV) in different populations. This study aimed to investigate the vitamin D-VDR pathway in PV in the Tunisian population. A serological study was carried out to determine the vitamin D status in newly diagnosed PV patients. CYP27B1, CYP24A1 and VDR mRNA expression was assessed using quantitative real-time PCR in peripheral blood mononuclear cells (PBMC) from untreated newly diagnosed and treated PV patients. In addition, a genetic study was accomplished on VDR polymorphisms to investigate the changes in VDR gene expression. Overall, the serological study confirmed the hypovitaminosis D in newly diagnosed PV patients. Vitamin D-VDR pathway gene expression showed downregulation of CYP27B1 and CYP24A1 mRNA in first-discovery patients compared to healthy controls, while VDR mRNA was highly expressed in newly diagnosed PV patients. Moreover, CYP27B1, CYP24A1 and VDR mRNA were significantly upregulated in chronic disease severity groups compared to mild disease groups. The genetic study showed low VDR gene expression in carriers of FokI > CC genotype, which was more frequent among PV patients, and FokI > C-TaqI > C-ApaI > A-polyA > A16 haplotype, suggesting that the VDR gene polymorphisms testing can provide useful information for PV treatment decision-making. In conclusion, our findings underline the impact of vitamin D-VDR pathway disruption in the PV pathophysiology in Tunisian patients.

Maternal inherited thrombophilia and recurrent pregnancy loss: a Tunisian study and review of literature.

Background: Inherited thrombophilia, mainly the Factor V Leiden (FVL) and Prothrombin mutation (PTM) are the most risk factors for venous thrombosis especially during pregnancy and was strongly associated with recurrent pregnancy loss (RPL), a devastating reproductive problem that affects more than 1% of couples who are trying to conceive. The frequencies also the correlation among these polymorphisms and RPL have been reported controversially in various populations. Objectives: In this study we evaluated the presence inherited thrombophilia amongst 35 Tunisian women with more than 2 miscarriages, referred to our genetic counseling. Methods: DNA was extracted from peripheral blood samples and PCR-RFLP was performed for the molecular diagnosis of mutation. Results: FVL and PTM were detected in 5.7 % and 2.9% respectively; in women with a particular history of early fetal loss and thrombotic events. Conclusion: This study emphasizes the importance of testing for FVL and FIIM in women with RPL; mainly in the context of thrombotic events. Multi-center collaboration is necessary to clarify the real impact of thrombotic molecular defects on the pregnancy outcome, to ascertain the effect of inherited thrombophilia on recurrent pregnancy loss and then to evaluate the appropriate therapeutic approach.

An unusual three-way translocation t(21;8;1)(q22;q22;q32) in a case of acute myeloid leukemia (M2).

Variant forms of the classic translocation t(8;21) are uncommon and account approximately 3% of all t(8;21)(q22;q22) in acute myeloid leukemia (AML) patients. These forms involve chromosomes 8, 21, and other chromosomes. Here we report a Tunisian patient with a complex rearrangement t(21;8;1)(q22;q22;q32) revealed by conventional chromosomal study at diagnosis. Fluorescence in situ hybridization study revealed the presence of the AML1-ETO chimeric gene on the derivative chromosome 8. To the best of our knowledge, this is the second case of t(21;8;1) of AML-M2 reported in the literature with the involvement of the same breakpoint at 1q32. This illustrates that this complex translocation is rarely encountered in AML and reinforces the fact that this region may harbour a critical gene candidate that may play an important role in the pathogenesis of AML. More cases are needed to elucidate its clinical features and prognosis.

Lack of Impact of the A1298C MTHFR on the Risk of Childhood Acute Lymphoblastic Leukemia: Evidence from a Meta-analysis.

To clarify the effect of the A1298C variant of methylenetetrahydrofolate reductase (MTHFR) gene on the risk of acute lymphoblastic leukemia (ALL), an updated meta-analysis was performed. Electronic literature search was carried out in PubMed to collect relevant articles. Pooled odds ratios (OR) and stratification analysis were achieved under different genetic comparison models, age and ethnicity. A total of 46 articles including 7020 cases and 12,114 controls were enrolled. Overall, no significant association was observed for the MTHFR A1298C variant on the risk of ALL in any genetic model test, when all the studies pooled together (OR ~ 1 0.91; p > 0.05). In subgroup analyses stratified by age and ethnicity, the MTHFR A1298C reduce the risk of ALL in adult under allele contrast (OR = 0.88; [0.72; 1.09], p = 0.23) mainly in Caucasian populations. The present meta-analysis provides evidence that the A1298C variant of MTHFR gene is unlikely to be a major risk gene for childhood ALL.

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.

Update meta-analysis from biomedical literature about MTHFR'polymorphisms and the CML' risk.

BACKGROUND: The MTHFR gene polymorphisms are closely related to the chronic myeloid leukemia (CML). Case-control studies have associated the MTHFR polymorphisms and susceptibility to CML but the results were not conclusive. AIM: To assess this association through an update meta-analysis. METHODS: A descriptive and qualitative study was conducted among students in the 6th year of the faculty during the academic year 2020/2021. The data were collected through a questionnaire written in french evaluating the teaching methods. A focus group of ten persons was led to understand better student's opinions. RESULTS: Totally, 17 and 12 case-control studies including CML cases and controls were enrolled in the meta-analysis respectively for C677T and A1298C polymorphism and CML risk. A poor association between the C677T (T vs C ; OR= 1,28; IC95%= [1,01;1,63]; p=0,04) and the one not significant between the A1298C (C vs A ; OR= 1,52; IC95%= [0,92; 2,51]; p= 0,1) polymorphisms and the CML risk for overall population were found. CONCLUSION: The results of this meta-analysis suggested no significant association between C677T and A1298C polymorphisms and CML risk leading to consider other factors such us folic acid intake, gene-gene and gene- environment interactions.

Germ Cell Tumors Revealing a Familial Persistent Müllerian Duct Syndrome.

Persistent Mullerian duct syndrome (PMDS) is a congenital disorder related to male sexual development. PMDS is usually diagnosed during an inguinal hernia cure. The diagnosis of PMDS following a testicular germ cell tumor is less common. We report the cases of three infertile male patients who were diagnosed with PMDS after surgery for germ cell tumors. They were 39, 27, and 37 years old men with a medical history of neglected cryptorchidism. All patients had a male karyotype and the ELISA test for the anti-Mullerian hormone was undetectable. Patients underwent chemotherapy followed by resection of residual mass in one patient. One patient is currently alive and disease-free. The two other patients died of systemic relapse. These cases highlight how early recognition and treatment of PMDS can prevent malignant germ cell tumors. The diagnosis of PMDS relies on a systemic assessment and analysis of mutations in the gene coding for AMH and AMHR-II. Key words: Persistent Müllerian duct syndrome (PMDS), anti mullerian hormone, germ cell neoplasm.

Cytogenetic Screening in Couples with Recurrent Pregnancy Loss: A Single-Center Study and Review of Literature.

CONTEXT: Recurrent pregnancy loss (RPL) is a devastating reproductive problem that affects more than 2% of couples who are trying to conceive. Chromosomal rearrangements in either carrier are a major cause of clinically recognized abortion. AIMS: The purpose of this study is to report the prevalence of chromosome abnormalities in RPL and provide clinical characteristics of couples with two and more miscarriages. SETTINGS AND DESIGN: Genetic counseling in laboratory of histology housed in a Faculty of Medicine of Sfax. MATERIALS AND METHODS: Karyotype was generated from the peripheral blood lymphocyte cultures and the cytogenetic analysis was performed using R-bands after heat denaturation and Giemsa (RHG) banding. A multiplex polymerase chain reaction wherever necessary was done. STATISTICAL ANALYSIS USED: SPSS version 17. RESULTS: A total of 104 couples with RPL were carried out in this study. The frequency of chromosomal rearrangements was 11.5%, three times more prevalent in men than women (P = 0.08). In addition, the prevalence of chromosomal anomalies increases according to the number of miscarriages (from 4.8% to 7.6%, with 2 or ≥3 miscarriages, respectively; P = 0.9). Finally, a particular familial adverse reproductive background was found in these carriers (P = 0.03). CONCLUSIONS: These data highlight that an RPL evaluation is appropriate after the second miscarriage and that cytogenetic evaluation is necessary for an accurate approach to elucidate the causes of RPL. Moreover, familial adverse reproductive backgrounds have an impact of being carrier of chromosome abnormalities and a larger study is mandatory to define reproductive characteristics of carriers.

Klippel-Feil syndrome: a review of the literature.

Klippel-Feil syndrome is a congenital defect in the formation or segmentation of the cervical spine. A wide spectrum of associated anomalies may be present. This heterogeneity has complicated clarification of the genetic causes and management of patient's with congenital vertebral fusion. In this review, we focussed on clinical heterogeneity; radiographic abnormalities and genetic etiology in Klippel-Feil syndrome. We insist on comprehensive evaluation and delineation of diagnostic and prognostic classes.

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 proteoglycans 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.