Biological sex and gender factors significantly influence the pathogenesis, progression, and treatment response in hematologic malignancies. This comprehensive review examines sex-specific differences in acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and multiple myeloma through systematic analysis of the peer-reviewed literature published between 2014–2024 and identified through structured searches of PubMed, Web of Science, and MEDLINE databases. Epidemiological data demonstrate higher disease incidence (57% male vs. 43% female in MM, 63% male vs. 37% female in AML hospitalizations for ages 18–39) and inferior outcomes in male patients across malignancy types (5-year relative survival rates of 48.8% vs. 60.4% in females with AML), while female patients exhibit superior survival despite experiencing greater treatment-related toxicities. Our analysis reveals consistent sex-specific patterns in molecular mechanisms, including distinct mutational profiles, differences in immune system function, and sex-based pharmacokinetic variations that collectively suggest the necessity for sex-differentiated treatment approaches. The review identifies reproducible patterns across diseases, particularly in cytogenetic and molecular characteristics, with females demonstrating favorable prognostic mutations in leukemias and higher rates of chromosomal abnormalities in multiple myeloma. Despite these identifiable patterns, significant knowledge gaps persist regarding the underlying mechanisms of sex-based outcome differences. Incorporating sex and gender considerations into precision medicine frameworks represents a critical advancement toward optimizing treatment strategies and improving clinical outcomes for patients with hematologic malignancies.

Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment landscape for hematologic malignancies. However, immune effector cell-associat

Pediatric solid tumors remain among the most treatment-refractory childhood malignancies, defined by biological features that have largely resisted the immunotherapeutic advances transforming adult oncology. Exceptionally low tumor mutational burden, sparse neoantigen landscapes, and profoundly immunosuppressive tumor microenvironments collectively undermine the T cell-dependent mechanisms on which most current immunotherapies depend. Yet the field is undergoing a meaningful shift. Anti-GD2 monoclonal antibodies have established a survival benchmark in high-risk neuroblastoma, and next-generation antibody-drug conjugates and bispecific T cell engagers targeting GD2, B7-H3, and GPC2 are extending the reach of antibody-based approaches across pediatric histologies. CAR T cell therapies have demonstrated clinical feasibility against multiple targets, with advanced engineering strategies, including cytokine armoring, bispecific constructs, and locoregional delivery, beginning to address fundamental barriers such as poor tumor infiltration, limited persistence, and antigen escape. Immune checkpoint inhibitors, while largely ineffective as monotherapy in unselected populations, induce durable responses in molecularly defined subsets such as mismatch repair-deficient and hypermutated tumors. Emerging platforms, including oncolytic virotherapy, NK cell engagers, and neoantigen vaccines, offer rational strategies to convert immunologically cold tumors into treatment-responsive phenotypes. Together, these advances point toward a future of combination immunotherapy tailored to the distinct immune biology of childhood cancers.

Gordon syndrome (Pseudohypoaldosteronism type II) is a rare autosomal dominant disorder characterized by hyperkalemia, hypertension, and metabolic acidosis. Among the four causative genes, CUL3 mutations produce the most severe phenotype, yet endocrine manifestations beyond growth delay remain poorly described. We report a 22-year-old male who presented with chronic hyperkalemia, hypertension, insulin resistance with steatohepatitis, and testicular hypoplasia with elevated gonadotropins, consistent with compensated primary testicular dysfunction. Genetic analysis identified a de novo heterozygous CUL3 c.1207-26A>G splice-site mutation resulting in exon 9 skipping. Treatment with hydrochlorothiazide normalized blood pressure and serum potassium while improving metabolic and hormonal abnormalities. Notably, these improvements reversed upon treatment discontinuation. This case suggests that certain endocrine manifestations in CUL3 -related Gordon syndrome may be secondary to chronic electrolyte imbalance rather than direct genetic effects, highlighting the importance of comprehensive endocrine evaluation and sustained thiazide therapy in affected patients.