Molecular Analysis of Patients With Myelodysplastic Neoplasms From a Single Academic Center
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background Comprehensive gene sequencing (NGS) has become an essential tool in the diagnosis and prognostic assessment of myeloid neoplasms (MN), and incorporated into WHO 2022 myelodysplastic neoplasms (MDS) classification and IPSS-M. Despite current recommendations, access to molecular testing remains limited in Brazil. This study aimed to characterize the molecular profile of patients with MDS and related MN who underwent NGS testing at our institution. Methods We performed a retrospective analysis of patients followed in a single public academic center in Brazil with diagnoses of MDS, chronic myelomonocytic leukemia (CMML), MDS with germline predisposition, and MDS/myeloproliferative neoplasm (MDS/MPN) overlap who underwent NGS testing between 2010 and 2026. Only Likely Pathogenic or Pathogenic (LP/P) variants, according to AMP/ASCO/CAP guidelines (2017) were considered. Four different NGS panels were used during the period: Ion Torrent (72 genes, 2022–2025), Illumina OncoReveal (58 genes, from 2025), Research Panel 1 (16 genes), and Research Panel 2 (159 genes). Results 59 patients underwent NGS testing; the median age was 66 years. Diagnoses included de novo MDS (n = 36, 61%), therapy-related MDS (n = 1, 2%), suspected germline predisposition syndromes (n = 5, 8%), CMML (n = 13, 22%), and MDS/MPN overlap (n = 5, 8%). Ion Torrent, Illumina, Research Panel 1 and 2 were used in 50%, 40%, 8%, and 2% of patients, respectively. Overall, LP/P variants were identified in 43 patients (73%). Among 37 patients with de novo or therapy-related MDS, at least one pathogenic mutation was identified in 60% of patients. SF3B1 (21%) was the most common, followed by U2AF1 and DNMT3A (8.9% each), and TP53 (7.1%). 32 MDS patients could be risk stratified (missing karyotype in 5). Eight patients (25%) had IPSS-R score ≥ 3.5 and another 8 (25%) had an IPSS-M score > 0, meeting our definition of high-risk disease. Molecular information changed risk stratification in 6 patients: 3 were reclassified from low to high risk and 3 from high to low risk. Interestingly, all three patients downstaged by IPSS-M had IPSS-R score of 3.5. Although this score was considered high risk according to our study definition, it corresponds to the intermediate-risk category in the original IPSS-R. It is also worth noting that none of these patients had any pathogenic mutation. At least 1 pathogenic mutation was found in 11 (84%) CMML patients. The most frequent mutations were SRSF2 and TET2 (21% each), frequently occurring together, followed by U2AF1 (6.9%) and ASXL1 (3.4%). NGS identified pathogenic variants in 3 of five patients with suspected germline predisposition syndromes, confirming 2 cases of GATA2 deficiency and 1 case of ANKRD26-related thrombocytopenia. In the MDS/MPN overlap cohort (n = 5), ASXL1 mutations were identified in 2 patients. Other mutations were SF3B1, JAK2, and PTPN11. Conclusions NGS identified clinically relevant molecular abnormalities in the majority of patients and resulted in prognostic reclassification in approximately one-fifth of evaluable MDS cases. In addition, molecular testing confirmed the diagnosis of germline predisposition syndromes in some patients. NGS is now routinely available at our institution, representing an important step to molecular diagnosis.
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223097539