Cytogenetic profile of myelodysplastic syndrome: A retrospective study

INTRODUCTION

Myelodysplastic syndromes (MDSs) represent a heterogeneous group of clonal hematopoietic disorders characterized by ineffective hematopoiesis, peripheral cytopenia, and an increased risk of transformation to acute myeloid leukemia.^[1] The disease primarily affects the elderly, although cases are increasingly recognized in younger populations in developing countries. The pathogenesis of MDS involves complex genetic alterations that disrupt normal hematopoietic stem cell differentiation and proliferation.^[2]

Cytogenetic abnormalities play a crucial role in the diagnosis, classification, prognosis, and therapeutic decision-making in MDS. Approximately 30–50% of patients exhibit clonal chromosomal abnormalities at diagnosis when analyzed by conventional karyotyping. The most frequently encountered cytogenetic abnormalities include deletions in the long arms of chromosomes 5q and 7q, monosomy 7, trisomy 8, and deletion of 20q. Among these, isolated del(5q) is associated with a distinct clinical entity and favorable response to lenalidomide therapy, while monosomy 7, complex karyotypes, and abnormalities of chromosome 17p are associated with adverse outcomes. The Revised International Prognostic Scoring System incorporates cytogenetic findings as a major determinant of disease risk stratification and survival prediction.^[3]

Fluorescence in situ hybridization (FISH) serves as a valuable complementary tool to conventional cytogenetics, particularly in cases with failed or inadequate metaphase yield, or to detect cryptic deletions that may not be evident on G-banding. The integration of conventional cytogenetics with FISH and, where feasible, molecular testing enhances diagnostic accuracy and risk assessment.

Studies from India have reported variable frequencies of cytogenetic abnormalities in MDS, often showing a relatively higher prevalence of poor-risk lesions such as monosomy 7 and complex karyotypes, and a younger median age at presentation compared with Western cohorts. These regional differences may reflect underlying genetic, environmental, or occupational factors, as well as referral bias in tertiary care settings.^[4,5]

Given the prognostic importance of cytogenetic findings and the limited Indian data from large cohorts, there is a need to document local cytogenetic patterns in MDS. The present retrospective study was undertaken to evaluate the spectrum and frequency of cytogenetic abnormalities in patients with MDS, using conventional karyotyping and confirmatory FISH analysis, and to compare these findings with previously reported national and international data.

In the present study, we are looking back at the cytogenetic profiles of patients referred to our laboratory from various parts of India. We analyzed how often chromosomal abnormalities show up using both traditional karyotyping and FISH, and then compared our findings with published data. By adding to the growing evidence from India, we hope to understand the genetic factors behind MDS in this specific context and how they relate to the prognosis.

MATERIAL AND METHODS

RESULTS

A total of 281 patients diagnosed with MDS were included in this retrospective analysis. The study cohort comprised males 154 (55%) and 127 (45%), with a male-to-female ratio of 1.2:1. The patients’ ages ranged from 11 to 89 years, with a mean age of 67.3 ± 10.4 years [Table 1]. Most of the cases were observed in the 5^th–7^th decades of life, consistent with the known age distribution of MDS [Table 1].

Cytogenetic findings

A cytogenetic study was carried out on 281 patients referred to our laboratory for chromosomal and FISH studies. Normal karyotype was present in 245 (87.0%), whereas abnormal karyotype was present in 36 (13.0%) [Figures 1-3]. The relatively low frequency of cytogenetic abnormalities, approximately 13% observed in our cohort, may be attributable to referral bias and suboptimal bone marrow cellularity.

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Figure 1: Myelodisplastic syndrome karyotype abnormality with 46,XX,del(5q),del(7q), del(20q), and t(8;17)(p23;p11.2).

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Figure 2: (a) Interphase FISH (two orange signals and two green) showing normal pattern, (b) Interphase FISH (one orange and one green signals) with del(5q), (c) Interphase FISH (two green signals and one orange) with del (7q), and (d) interphase FISH (one orange and two green signals) Del (20q). FISH: Fluorescence in situ hybridization

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Figure 3: MDS karyotype showing abnormality with 47,X,inv(Y)(p11q11),+8.

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The most frequent chromosomal abnormalities detected/risk categories were:

• Deletion 5q (del(5q)) – Fifteen cases (41%)/Very good/good risk

• Monosomy 7/del(7q) – Twenty-five cases (69%)/Poor/very poor risk

• Trisomy 8 (+8) – Three cases (8.3%)/Intermediate risk:

• Deletion 20q (del(20q)) – Ten cases (28%)/Intermediate risk:

• Complex karyotype – Two cases (6%), often involving combinations of del(5q), monosomy 7, and structural rearrangements of chromosomes 8q+ and inv 9, respectively/poor risk

DISCUSSION

In current study, cytogenetic abnormalities were identified in 13% of patients, while 87% demonstrated a normal karyotype. Although this incidence is lower than that reported in some Western studies and Indian studies. These differences may be attributable to variations in disease biology, referral bias, sample quality, and diagnostic infrastructure, as well as the limited availability of genome-wide molecular testing in routine clinical practice. Importantly, the incorporation of FISH analysis enabled the detection of abnormalities in patients with normal metaphase cytogenetics, thereby reinforcing its value as a complementary diagnostic tool in MDS.

Chromosome 7 abnormalities, including monosomy 7 and del(7q), constituted the most frequent cytogenetic aberrations in our cohort and were predominantly associated with poor and very poor IPSS-R risk categories.^[7] These findings have significant clinical relevance, as chromosome 7 abnormalities are well-established markers of poor survival and an increased risk of leukemic transformation. The relatively high prevalence of monosomy 7/del(7q) observed in this study may reflect delayed diagnosis and referral bias toward a higher proportion of high-risk patients, a pattern commonly encountered in resource-limited healthcare settings.

Deletion of the long arm of chromosome del(5q) was the most frequent favourable-risk abnormality and was consistently classified within the good-risk group according to the IPSS-R. Isolated del(5q) MDS is recognized as a distinct clinic-pathological entity characterized by an indolent clinical course and a predictable response to lenalidomide. The identification of this abnormality therefore carries direct therapeutic implications, underscoring the critical role of cytogenetic analysis in enabling risk-adapted, individualized treatment strategies in MDS.^[8]

The frequencies of intermediate-risk abnormalities, including del(20q) and trisomy 8, were comparatively low. The prognostic significance of trisomy 8 remains biologically heterogeneous, with outcomes influenced by accompanying molecular alterations and immune-mediated mechanisms. Isolated del(20q) has traditionally been associated with a favourable prognosis; however, its impact becomes less favourable in the presence of additional cytogenetic or molecular abnormalities. The classification of these aberrations as intermediate risk in our study is consistent with IPSS-R guidelines.

Complex karyotypes were infrequent but uniformly associated with poor prognostic subgroups. These cases typically involved multiple structural and numerical chromosomal abnormalities, reflecting a high degree of genomic instability and an adverse response to conventional therapies. Despite their low frequency, the presence of complex karyotypes indicates aggressive disease biology and an overall poor prognosis.^[9]

A major strength of this study lies in the combined use of conventional cytogenetics and targeted FISH, which enhanced the overall diagnostic yield. However, certain limitations must be acknowledged. The retrospective design precludes the establishment of definitive associations between cytogenetic and molecular aberrations. Additionally, key clinical endpoints such as overall survival, leukemic transformation, and treatment response could not be evaluated. Prospective studies integrating cytogenetic analysis with comprehensive molecular profiling are therefore warranted.

In current study, cytogenetic abnormalities were identified in 13% of patients, while 87% demonstrated a normal karyotype. Although this incidence is lower than that reported in some Western studies and Indian studies. These differences may be attributable to variations in disease biology, referral bias, sample quality, and diagnostic infrastructure, as well as the limited availability of genome-wide molecular testing in routine clinical practice. Importantly, the incorporation of FISH analysis enabled the detection of abnormalities in patients with normal metaphase cytogenetics, thereby reinforcing its value as a complementary diagnostic tool in MDS.

Chromosome 7 abnormalities, including monosomy 7 and del(7q), constituted the most frequent cytogenetic aberrations in our cohort and were predominantly associated with poor and very poor IPSS-R risk categories.^[7] These findings have significant clinical relevance, as chromosome 7 abnormalities are well-established markers of poor survival and an increased risk of leukemic transformation. The relatively high prevalence of monosomy 7/del(7q) observed in this study may reflect delayed diagnosis and referral bias toward a higher proportion of high-risk patients, a pattern commonly encountered in resource-limited healthcare settings.

Deletion of the long arm of chromosome del(5q) was the most frequent favourable-risk abnormality and was consistently classified within the good-risk group according to the IPSS-R. Isolated del(5q) MDS is recognized as a distinct clinic-pathologic

CONCLUSION

In conclusion, this study provides a detailed characterization of cytogenetic abnormalities in an Indian cohort of patients with MDS and reaffirms the prognostic significance of chromosome 7 abnormalities and del(5q) within the IPSS-R framework. Our findings support the routine use of combined karyotyping and FISH analysis in the diagnostic evaluation of MDS and contribute to a broader understanding of MDS biology in a global context.