Cytogenetic and Molecular Abnormalities in Hematologic Malignancies: A Comprehensive Review of Mechanisms, Biomarkers, and Therapeutic Advances

Abstract

Cytogenetic and molecular abnormalities are fundamental drivers of hematologic malignancies, shaping disease classification, prognosis, and therapeutic decision-making. Over the past two decades, advances in next-generation sequencing and precision medicine have substantially expanded our understanding of the genetic and epigenetic mechanisms underlying leukemia, lymphoma, and related disorders. To provide a comprehensive synthesis, a narrative review of peer-reviewed literature published between January 2000 and June 2025 was conducted across PubMed, Scopus, Embase, and Web of Science. Eligible studies included original research, systematic reviews, and metaanalyses reporting on cytogenetic and molecular mechanisms, diagnostic biomarkers, and therapeutic innovations in hematologic malignancies. Findings from this review highlight recurrent chromosomal abnormalities such as t(9;22) BCR-ABL1 in chronic myeloid leukemia, t(15;17) PML-RARA in acute promyelocytic leukemia, and del(17p)/TP53 mutations in chronic lymphocytic leukemia as pivotal prognostic and therapeutic markers. Molecular mutations including FLT3, NPM1, IDH1/2, and DNMT3A were consistently linked to poor or intermediate outcomes in acute myeloid leukemia, while MYD88 and EZH2 mutations were frequently observed in B-cell lymphomas. Diagnostic modalities such as fluorescence in situ hybridization, PCR, and next-generation sequencing were shown to improve classification and treatment guidance. Importantly, targeted therapies including tyrosine kinase inhibitors, FLT3 and IDH inhibitors, and epigenetic modulators have significantly transformed patient outcomes, although access and treatment resistance remain major barriers, especially in low-resource settings. This review underscores the need for molecularly informed diagnostic algorithms, wider integration of next-generation sequencing into standard care, and expanded access to targeted therapies. Strengthening laboratory infrastructure, establishing region-specific treatment guidelines, and enhancing equitable access to molecular testing and therapy are essential steps toward improving outcomes. Overall, cytogenetic and molecular profiling has redefined the management of hematologic malignancies, but disparities in access and the emergence of resistance highlight the importance of continued innovation, biomarker discovery, and personalized therapeutic strategies to achieve durable patient benefit.