Abdul Qader Mima

Background:

Diagnostic cytogenetics has evolved from a purely descriptive discipline into an integral component of precision hematology. Traditional G-banded karyotyping, while foundational, is inherently limited by its microscopic resolution and must increasingly be interpreted alongside molecular techniques—fluorescence in situ hybridization (FISH), chromosomal microarray (CMA), next-generation sequencing (NGS), and optical genome mapping (OGM). The 2024 edition of the International System for Human Cytogenomic Nomenclature (ISCN 2024) was developed to standardize the reporting of findings across these heterogeneous platforms within a single, interoperable nomenclature framework.

Objective:

This review examines the structural and conceptual updates introduced by ISCN 2024 and evaluates their clinical significance in guiding the diagnosis, risk stratification, and therapeutic management of acute and chronic hematological malignancies, in alignment with the WHO 5th Edition (2022) and International Consensus Classification (ICC 2022).

Discussion:

ISCN 2024 introduces several substantive innovations: a formal prefix (ogm) for genome-mapping data; standardized double-colon (::) notation for gene fusions (e.g., BCR::ABL1, PML::RARA), replacing ambiguous legacy formats; refined criteria for describing complex genomic rearrangements such as chromothripsis and chromoplexy; and explicit integration of molecular breakpoints and GRCh38-based coordinates within the conventional karyotype line. Critically, the system maintains a clear distinction between cytogenetic-level resolution (visible banding) and molecular-level resolution (nucleotide coordinates), preventing artificial inflation of precision unsupported by the analytic method employed. Clinically, ISCN-defined cytogenetic entities directly inform prognostic stratification (e.g., ELN/NCCN risk categories in AML) and therapeutic selection—illustrated by ATRA/ATO-based differentiation therapy in PML::RARA-positive acute promyelocytic leukemia, and tyrosine kinase inhibitor therapy in BCR::ABL1-positive leukemias. Serial cytogenetic monitoring further supports assessment of clonal evolution, measurable residual disease, and the timing of allogeneic hematopoietic stem cell transplantation. Nonetheless, ISCN findings must be interpreted within a multidisciplinary, multiparametric framework rather than as an isolated determinant of treatment.

Conclusion:

ISCN 2024 represents a substantial methodological advance in unifying cytogenetic and genomic reporting, thereby strengthening the reproducibility and clinical utility of chromosomal nomenclature. Its adoption necessitates parallel advances in laboratory informatics infrastructure and multidisciplinary interpretive expertise, while automation tools (bioinformatics, natural language processing) may assist—but should not replace—expert cytogenetic review.

Keywords:

ISCN 2024; cytogenomics; karyotype; gene fusion nomenclature; acute myeloid leukemia; chromothripsis; precision hematology; hematopoietic stem cell transplantation