Cytogenetic profiling in myelodysplastic syndromes: Perspective on an Indian cohort

Dear Editor,

The manuscript entitled “Cytogenetic profile of myelodysplastic syndrome: A retrospective study” (JHAS_81_2025) addresses a clinically important dimension of myelodysplastic syndromes (MDSs), which are clonal hematopoietic disorders characterized by cytopenias and risk of progression to acute myeloid leukemia, in which cytogenetic abnormalities play a central role in diagnosis, classification, and prognostic stratification, forming an integral component of risk assessment models such as the Revised International Prognostic Scoring System (IPSS-R).^[1,2]

This retrospective study provides valuable insight into the cytogenetic spectrum observed in an Indian cohort – an underrepresented population in large genomic and cytogenetic datasets. The authors should be commended for compiling real-world data from a resource-constrained setting and for integrating conventional karyotyping with fluorescence in situ hybridization (FISH). The identification of recurrent abnormalities such as del (5q), monosomy 7, trisomy 8, and complex karyotypes reinforces the biological heterogeneity of MDS and highlights the prognostic importance of cytogenetic stratification. In particular, chromosome 7 abnormalities and complex karyotypes are well recognized for their association with inferior survival and higher rates of leukemic transformation, directly influencing therapeutic decisions, including hypomethylating therapy and consideration of allogeneic transplantation in eligible patients.^[2,3] A notable strength of the study is its focus on region-specific cytogenetic patterns. Geographic variation in disease biology, referral patterns, and environmental exposures may influence cytogenetic distributions, making such data highly relevant for local clinical practice. The detailed presentation of karyotypic abnormalities enhances transparency and allows independent interpretation.

However, certain aspects would benefit from further clarification. The reported cytogenetic abnormality rate of 13% is notably lower than the 40–60% frequency commonly described in literature when conventional cytogenetics and FISH are combined, warranting further contextual clarification.^[4] While this does not invalidate the findings, a more detailed discussion of potential contributing factors – such as referral bias toward lower-risk disease, marrow hypocellularity, limited probe panels, or culture-related technical factors – would provide important context. Clarification regarding the FISH probe panel employed, criteria for positivity, and whether FISH analysis was applied universally or selectively would enhance interpretability and reproducibility. Furthermore, integration of clinical variables such as World Health Organization subtype, IPSS-R risk distribution, cytopenia severity, and limited outcome data would significantly improve clinical correlation. The inclusion of younger patients is noteworthy but raises the possibility of inherited bone marrow failure syndromes or secondary MDS; clarification regarding exclusion criteria would be helpful. In addition, a clearer definition of complex karyotype using standard criteria and distinction of constitutional variants from clonal abnormalities would improve precision. Finally, although primarily descriptive, inclusion of basic statistical comparisons would enhance analytical depth. Future studies incorporating molecular profiling – given the recognized prognostic impact of mutations such as TP53, ASXL1, and SF3B1 and their integration into contemporary classifications would further refine risk stratification.^[3,4]

In summary, this study reinforces the enduring relevance of conventional cytogenetics in MDS and contributes meaningful regional data. We commend the authors for this valuable contribution, and with enhanced methodological clarity and clinical integration, such work can further improve the interpretation and applicability of cytogenetic findings while advancing understanding of MDS biology in diverse healthcare settings.