Haematological malignancies comprise a heterogeneous group of cancers originating from haematopoietic and lymphoid tissues, including leukaemia, lymphoma, and multiple myeloma. These disorders are characterised by clonal proliferation of abnormal blood cells that disrupt normal haematopoiesis and immune function.¹ Leukaemias are classified as acute or chronic and arise from myeloid or lymphoid lineages, whereas lymphomas develop within lymphatic tissues and are broadly categorised as Hodgkin or non-Hodgkin types.² Multiple myeloma originate from malignant plasma cells in the bone marrow and presents with distinct clinical manifestations.³

Globally, these malignancies impose a substantial epidemiological burden, with incidence influenced by age, genetic predisposition, and environmental exposures. Common clinical features include anaemia, recurrent infections, lymphadenopathy, and bone lesions.^4,5 Their marked biological heterogeneity complicates diagnosis and prognostication, making molecular and cytogenetic abnormalities central to disease classification and risk stratification.^6,7

Cytogenetic analysis has long been integral to the diagnosis and classification of haematologic neoplasms. Conventional techniques, such as G-banded karyotyping and fluorescence in situ hybridisation, detect chromosomal abnormalities, including translocations, deletions, and duplications, which carry diagnostic and prognostic significance, exemplified by the Philadelphia chromosome in chronic myeloid leukaemia and characteristic translocations in acute lymphoblastic leukaemia.⁸

However, these approaches have inherent limitations. Karyotyping requires actively dividing cells and has relatively low resolution, while fluorescence in situ hybridisation provides targeted analysis but lacks genome-wide coverage.⁹ Advances in molecular cytogenetics, particularly array comparative genomic hybridisation (array CGH), have addressed these constraints by enabling high-resolution, genome-wide detection of chromosomal imbalances¹⁰ (Figure 1).

Array CGH is a high-resolution molecular cytogenetic technique that detects genome-wide copy number alterations (CNAs), including deletions, duplications, and amplifications, through competitive hybridisation of labelled test and reference DNA to microarray probes.^10,11 Unlike conventional cytogenetic methods, array CGH does not require dividing cells, allowing analysis of non-dividing or archived samples and detection of copy number variations at kilobase-level resolution.¹²

This technology has become widely applied in cancer research to characterise genomic complexity and identify alterations associated with tumour behaviour, therapeutic response, and clinical outcome.^13,14,15 In haematological malignancies, array CGH refines cytogenetic evaluation and supports more precise diagnostic and prognostic assessment^12,16,17 (Figure 2).

Array CGH contributes to molecular subclassification across haematologic malignancies. In diffuse large B-cell lymphoma, which accounts for over 30% of adult lymphomas and exhibits substantial heterogeneity,⁷² recurrent genomic gains and losses affecting ≥ 20% of cases define subtype-specific genomic signatures correlated with gene expression profiles and clinical outcomes.^{72,73,74,75,76}

In peripheral T cell lymphoma, unspecified, high-density array CGH identifies recurrent gains at 7p and 7q and deletions at 9p21.3, associated with adverse prognosis.^77,78 Comparative profiling with adult T-cell leukaemia/lymphoma reveals shared genomic features that support refined classification.⁷⁸

Additional contributions include genomic characterisation of myelodysplastic syndromes, myeloproliferative neoplasms, and chronic myelomonocytic leukaemia.^{79,80,81,82,83} In chronic myelomonocytic leukaemia, recurrent abnormalities such as trisomy 8, deletion 20q, RAS and RUNX1 mutations, and cryptic inversions including USP16-RUNX1 fusion illustrate genomic complexity and disease heterogeneity.^{17,49,84,85,86,87}

Array CGH provides genome-wide, high-resolution detection of CNAs, surpassing conventional cytogenetics for submicroscopic abnormalities.^10,12,16 While balanced rearrangements require complementary approaches, combined use of cytogenetic and molecular technologies increases diagnostic yield and refines molecular subtyping.

Integration with next-generation sequencing enables detection of point mutations, small insertions and/or deletions, and structural variants, providing a comprehensive genomic profile that improves disease classification and therapeutic targeting.^{88,89,90,91,92,93,94,95,96} Emerging developments, including single-cell array CGH, enhanced probe density, and advanced bioinformatic algorithms, further improve detection of clonal evolution and complex genomic architecture.^{97,98,99,100,101,102}

International cytogenomic guidelines recommend array CGH as a complementary diagnostic tool, emphasising assay validation, quality control, and standardised interpretation.^{12,103,104,105} Successful implementation requires integration with clinical, pathological, and molecular data to ensure diagnostic reliability.

Adoption may be limited by infrastructure requirements, costs, and the need for specialised expertise.¹² Nevertheless, clinical studies in paediatric leukaemia and chronic lymphocytic leukaemia demonstrate that array CGH identifies additional abnormalities beyond conventional cytogenetics, improving molecular characterisation and prognostic stratification.^44,106,107

Array CGH has expanded understanding of tumour biology by identifying subclonal CNAs and tracking clonal evolution, thereby elucidating mechanisms of relapse and therapeutic resistance.^{68,104,108,109} It has also uncovered cryptic deletions, novel CNAs, and gene fusions affecting oncogenes, tumour suppressors, and regulatory RNAs.^{10,110,111,112,113,114,115} These discoveries contribute to biomarker identification and the development of targeted therapeutic strategies, reinforcing their role in translational haematology research.¹¹⁶

Array CGH cannot detect balanced rearrangements or very small sequence variants, necessitating complementary molecular approaches.¹¹⁷ Integration with sequencing-based, transcriptomic, and proteomic analyses enables more comprehensive genomic characterisation.^78,118 Continued improvements in probe density, hybridisation chemistry, computational algorithms, and single-cell applications are expected to enhance sensitivity and analytical precision.^119,120

Incorporation of array CGH into clinical practice enables identification of clinically actionable genomic alterations and refined prognostic stratification, supporting individualised therapeutic strategies and improved patient management.^12,121

Array CGH has substantially advanced cytogenetic evaluation of haematologic malignancies by enabling high-resolution, genome-wide detection of DNA CNAs. When integrated with conventional cytogenetics and sequencing technologies, it enhances diagnostic accuracy, prognostic assessment, molecular subclassification, and personalised treatment planning. Continued technological refinement, standardisation, and integrative genomic strategies will further consolidate its role in precision haematologic oncology.