Among the transcriptional dependencies that sustain leukemic identity in acute myeloid leukemia (AML), the menin–KMT2A chromatin complex has emerged as a central regulatory node. The scaffold protein menin, encoded by MEN1, facilitates transcriptional activation of HOX and MEIS family genes during normal hematopoietic development. In AML, this physiologic and developmentally regulated role is co-opted to sustain constitutive HOX/MEIS-driven programs that block differentiation and maintain leukemic potential. Although dependency on menin is most clearly established in KMT2A-rearranged and NPM1-mutated AML, this vulnerability appears to arise from a shared transcriptional state characterized by persistent HOX activation rather than from any single genetic alteration. Pharmacologic disruption of the menin-KMT2A interaction collapses stemness-associated transcriptional networks, promotes myeloid differentiation, and attenuates leukemic self-renewal. Clinical activity observed with menin inhibitors provides translational validation of this dependency and establishes menin inhibition as a differentiation-based therapeutic strategy. In this review, we examine the molecular basis of menin-dependent transcriptional regulation in AML and its implications for therapeutic targeting with menin inhibitors and resistance to therapy.

Idiopathic granulomatous mastitis (IGM) is an inflammatory-mediated rare disease that can be linked to rare manifestations. Erythema nodosum (EN) and polyarthritis, seen in a multitude of autoinflammatory and autoimmune diseases, have been rarely linked to IGM. Despite the cause of IGM being unclear, Corynebacterium infections are thought to play a role in the pathophysiology of IGM. Unusually, IGM has a relapsing and remitting course, which also applies to its systemic manifestations. As such, we present a case of IGM in a middle-aged lady who was initially thought to have Corynebacterium-containing unilateral abscesses for which drainage was performed. However, several abscesses devoid of bacterial growth started recurring, and the disease course was complicated by EN and polyarthritis. IGM, EN, and polyarthritis eventually resolved and were managed with symptomatic treatment.

Background: In the era of precision medicine, Next-Generation Sequencing (NGS) has emerged as an important tool for identifying targetable mutations and tailoring treatment options. Yet the Middle East and North Africa (MENA) lags behind in adopting this technology. This study aims to demonstrate the transformative potential of molecular profiling in the region. Methods: This retrospective study reviewed cancer patients at the American University of Beirut Medical Centre, comparing outcomes between those who received NGS-based treatment adjustments (NBTAs) and those who did not. Results: The study enrolled 180 patients, including those with non-small-cell lung cancer (21.2%), sarcomas (20%), gastrointestinal malignancies (23.3%), breast cancer (10.6%), and other cancers (24.9%); 58.3% had stage 4 cancer at diagnosis. Before molecular profiling, 20.6% had stable disease, 21.7% showed partial response, and 57.8% had progressive disease. Most (96%) had received treatment, mainly systemic (90%), with chemotherapy (89%) being the most common. Forty patients (22.2%) underwent NGS-based treatment adjustments (NBTAs). Post-NGS, targeted therapies increased from 35% to 43% and immunotherapies from 14% to 18%. Mutations were detected in 98% of patients, with a median of four mutations per patient. NBTA patients had a median overall survival of 59 months, compared to 23 months for non-NBTA patients (p = 0.096), and significantly improved progression-free survival (5.32 vs. 3.28 months, p = 0.023). Conclusions: The use of large-scale molecular profiling to guide treatment adjustments promises advancements in patient care. Integrating NGS into clinical practice correlates with improved PFS, calling for a broader adoption of its use in the MENA region.

Background: Sarcomas are rare, aggressive malignancies with limited therapeutic options in advanced stages. This is the first real-world study in the MENA region evaluating the clinical utility of Next-Generation Sequencing (NGS) in guiding sarcoma treatment and improving outcomes. Methods: We retrospectively reviewed sarcoma patients who underwent NGS at a major referral center (2021–2024), comparing clinical and molecular outcomes between those who received NGS-based treatment adjustments (NBTA) and those who did not. Results: Seventy-eight patients were included (60% male; median age 44 years). Soft tissue sarcomas accounted for 70.5% of cases (n = 55), while bone sarcomas represented 29.5% (n = 23). Prior to NGS, 64.1% of patients had received a median of one line of systemic therapy. NGS was performed late in the disease course in 73% of cases. At least one mutation was detected in 87% (median 3 mutations). Targetable alterations were identified in 33% at the time of testing, rising to 42% with updated genomic knowledge and therapeutic advances. Overall, 20.5% received NBTA. Among non-NBTA patients, 67% had no actionable targets, 17% had no detectable mutations, and 16% were ineligible due to cost, limited access, or clinical deterioration. Tumor Mutational Burden was low in 79%, intermediate in 19%, and high in 2%, and all tumors were microsatellite stable. Patients receiving NBTA had a longer median Progression-Free Survival (9 vs. 2 months; p = 0.023). Median Overall Survival was longer in the NBTA group (74 vs. 48 months), though not statistically significant (p = 0.207). Genomic alterations were subtype-specific: EWSR1 rearrangements (Ewing and Desmoplastic small round cell tumors), CDK4 and MDM2 amplifications (Liposarcoma and Osteosarcoma), TP53 and RB1 mutations (Leiomyosarcoma), CDKN2A/B deletions (Undifferentiated Pleomorphic Sarcoma and Chondrosarcoma), and SS18 rearrangements (Synovial Sarcoma). Conclusions: Genomics-guided therapy in sarcoma is feasible and impactful. Expanding timely access to molecular profiling is essential for advancing precision oncology in the MENA region.

Enfortumab vedotin (EV), pembrolizumab, and EV plus pembrolizumab (EV/P) have rapidly reshaped the treatment landscape of advanced urothelial carcinoma, but toxicity increasingly determines treatment delivery, treatment continuity, and real-world benefit. As EV/P moves into broader clinical use, clinicians must distinguish adverse events related to antibody-drug conjugate exposure from immune-mediated toxicities and recognize syndromes in which both mechanisms may contribute. In this practical, mechanism-informed review, we synthesize pivotal trials, mature follow-up reports, and representative real-world cohorts describing the safety of EV monotherapy, pembrolizumab monotherapy, and EV/P in urothelial carcinoma. Because adverse-event reporting and ascertainment are heterogeneous across studies, including differences in preferred terms, composite categories, grading frameworks, and treatment-related versus all-cause reporting, we emphasize clinically interpretable patterns rather than pooled estimates. Enfortumab vedotin monotherapy is characterized by cutaneous toxicity, peripheral neuropathy, hyperglycemia, dysgeusia, and ocular events, including early epithelial/metabolic events and cumulative neuropathy. Pembrolizumab monotherapy has a lower overall high-grade toxicity burden but is defined by immune-mediated endocrinopathies, pneumonitis, hepatitis, colitis, and nephritis. Combination therapy produces a predictable overlap of these toxicity domains, creating diagnostic and management challenges for syndromes such as skin toxicity, diarrhea, fatigue, and pulmonary symptoms. We provide comparative visual toxicity signatures, regimen-specific summary tables, temporal toxicity mapping, and a pragmatic attribution framework that classifies events as EV-predominant, immune-predominant, overlap/indeterminate, or high-risk requiring initial interruption of both agents. This review aims to support bedside recognition, provisional attribution, early management, and safer implementation of EV/P in contemporary urothelial carcinoma practice.