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Acute lymphoblastic leukemia (ALL) is a heterogeneous malignancy characterized by various genomic alterations playing a crucial role in disease classification, prognosis, and response to treatment. However, molecular diagnosis and effective management of this hematological malignancy remain a major challenge, particularly in developing countries, including Tunisia. In this study, we aimed to conduct a detailed analysis of copy number alterations (CNAs) associated with ALL in a cohort of 60 primary samples from Tunisian patients. Using multiplex ligation-dependent probe amplification (MLPA), major genetic lesions, including IKZF1 , CDKN2A/2B , PAX5 , ETV6 , BTG1, and genes located in the PAR1 region, were analyzed and their associations with clinical and laboratory features, as well as survival outcomes, were also evaluated. Our analysis revealed that 70% of patients had deletions and/or amplifications in at least one gene. The most frequently observed deletions were in CDKN2A/2B (33.3%, n = 20), IKZF1 (30%, n = 18), and PAX5 genes (25%, n = 15). BTG1 deletions were significantly associated with female gender, IKZF1 deletions were more frequent in adult patients, in those with elevated white blood cell (WBC) counts, and in cases involving the BCR::ABL1 translocation, while duplications of the PAR1 region were significantly associated with hyperdiploïdy. Regarding treatment response, cases of IKZF1 deletions showed a significant association with poor glucocorticoid response (GC) at day 8 of treatment and positive minimal residual disease (MRD) rates at days 33 and 63, particularly in B-ALL cases. Furthermore, patients with IKZF1 deletions were associated with significantly lower survival rates in both univariate and multivariate analyses compared to those without these deletions. Additionally, the integration of IKZF1 deletion status into risk stratification models revealed markedly different survival outcomes, highlighting its potential interest in developing new stratification algorithms. These results underscore the critical importance of molecular profiling, particularly IKZF1 status, for improving outcomes in ALL patients in Tunisia.

This study aimed to investigate azole resistance mechanisms in which involve 51A and 51B genes. Real-time Reverse Transcriptase qPCR method was applied to determine the overexpression of 51A and 51B genes for 34 isolates. PCR sequencing of these two genes was used to detect the presence of gene mutations. Susceptibility test found sensitivity to voriconazole (VOR) in all strains. 14.7% and 8.8% of isolates were resistant to itraconazole (IT) and posaconazole (POS), respectively, with a cross-resistance in 5.8%. For the double resistant isolates (IT/POS), the expression of 51A was up to 17-fold higher. PCR sequencing showed the presence of 2 mutations in 51A: a synonymous point mutation (P61P) in eight isolates, which did not affect the structure of CYP51A protein, and another non synonymous mutation (G206L) for only the TN-33 strain (cross IT/POS resistance) causing an amino acid change in the protein sequence. However, we noted in 51B the presence of the only non-synonymous mutation (L177G) causing a change in amino acids in the protein sequence for the TN-31 strain, which exhibits IT/POS cross-resistance. A short single intron of 67 bp was identified in the 51A gene, whereas three short introns of 54, 53, and 160 bp were identified in the 51B gene. According to the models provided by PatchDock software, the presence of non-synonymous mutations did not affect the interaction of CYP51A and CYP51B proteins with antifungals. In our study, the overexpression of the 51A and 51B genes is the primary mechanism responsible for resistance in collection. Nevertheless, other resistance mechanisms can be involved.

Abstract Objective Biclonal gammopathies (BGs) are rare situations characterized by the production of 2 monoclonal proteins. There are no available data on BGs in North Africa. We aimed to estimate the prevalence of BGs in our population and describe their clinical and laboratory features. Methods We conducted a 31-year retrospective study including patients with persistent double monoclonal bands based on the results of immunofixation/immunoelectrophoresis. Results A total of 35 patients with available clinical data (sex ratio, M/F = 1.53; mean age, 70 ± 10.87 years [range, 45–90 years]) were included. The main associated conditions were multiple myeloma (MM) (40%), BG of undetermined significance (BGUS) (34%), and lymphoproliferative diseases (23%). Only one-third of the patients had 2 monoclonal spikes on serum protein electrophoresis. The most common paraprotein combinations were immunoglobulin (Ig)G-IgG (25%) and IgG-IgA (23%) with different light chains in one-half of the cases. The mean follow-up was 25.6 months (median, 12 months). No BGUS evolved into a malignant disease. Conclusion BGs are rare in clinical laboratory routine but must be accurately identified by the pathologist. Our cohort is characterized by a high prevalence of BGUS compared with MM.