Combining metaphase cytogenetics with single nucleotide polymorphism arrays can improve the diagnostic yield and identify prognosis more precisely in myelodysplastic syndromes

Abstract

Background Myelodysplastic syndromes (MDS) encompass a group of heterogeneous haematopoietic stem cell malignancies characterised by ineffective haematopoiesis, cytological aberrations, and a propensity for progression to acute myeloid leukaemia. Diagnosis and disease prognostic stratification are much based on genomic abnormalities. The traditional metaphase cytogenetics analysis (MC) can detect about 40–60% aberrations. Single-nucleotide polymorphism arrays (SNP-A) karyotyping can detect copy number variations with a higher resolution and has a unique advantage in detection of copy number neutral loss of heterozygosity (CN-LOH). Combining these two methods may improve the diagnostic efficiency and accuracy for MDS. Methods We retrospectively analysed the data of 110 MDS patients diagnosed from January 2012 to December 2019 to compare the detection yield of chromosomal abnormalities by MC with by SNP-A, and the relationship between chromosomal abnormalities and prognosis. Results Our results showed that SNP-A improved the detection yield of chromosomal aberrations compared with MC (74.5 vs. 55.5%, p < .001). In addition, the positive yield could be further improved by combining MC with SNP-A to 77.3%, compared with MC alone. Univariate analysis showed that age >65 years, bone marrow blasts ≥5%, with acquired CN-LOH, new aberrations detected by SNP-A, TGA value > the median (81.435 Mb), higher risk by IPSS-R-MC, higher risk by IPSS-R-SNP-A all had poorer prognosis. More critically, multivariable analysis showed that age >65 years and higher risk by IPSS-R-SNP-A were independent predictors of inferior OS in MDS patients. Conclusion The combination of MC and SNP-A based karyotyping can further improve the diagnostic yield and provide more precise prognostic stratification in MDS patients. However, SNP-A may not completely replace MC because of its inability to detect balanced translocation and to detect different clones. From a practical point of view, we recommend the concurrent use of SNP-A and MC in the initial karyotypic evaluation for MDS patients on diagnosis and prognosis stratification. KEY MESSAGES SNP-A based karyotyping can further improve the MDS diagnostic yield and provide more precise prognostic stratification in MDS patients. Acquired CN-LOH is a characteristic chromosomal aberration of MDS, which should be integrated to the diagnostic project of MDS. The concurrent use of SNP-A and MC in the initial karyotypic evaluation for MDS patients can be recommended.

Refined cytogenetic IPSS‐R evaluation by the use of SNP array in a cohort of 290 MDS patients

“…SNP array was previously reported as a suitable and effective methodology to determine the cytogenetic profile of MDS patients by allowing the detection of the majority of relevant abnormalities 8–10 . Although combining both methodologies was shown to improve overall results as well as diagnostic accuracy for MDS, 11 performing both tests standardly for each newly diagnosed patient result in a particularly costly and time consuming approach, which turns out to be truly beneficial only for a small number of clinical cases.…”

“…SNP array was previously reported as a suitable and effective methodology to determine the cytogenetic profile of MDS patients by allowing the detection of the majority of relevant abnormalities. [8][9][10] Although combining both methodologies was shown to improve overall results as well as diagnostic accuracy for MDS, 11 performing both tests standardly for each newly diagnosed patient result in a particularly costly and time consuming approach, which turns out to be truly beneficial only for a small number of clinical cases. Moreover, despite the successful MDS characterization by the use of SNP array and the introduction of the technology into the diagnostic workup of MDS patients, a clear cytogenetic IPSS-R comparison and evaluation of its clinical usefulness was only performed on a small patient cohort so far.…”