{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T13:15:51Z","timestamp":1777900551704,"version":"3.51.4"},"reference-count":23,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Peripheral cytopenia occurs in approximately 2% of the population; however, in up to 0.9%, no cause is identified by conventional tests. Next-Generation Sequencing (NGS) detects somatic variants consistent with clonal hematopoiesis (CH). We aimed to determine the prevalence of CH and pre-myelodysplastic syndrome (pre-MDS) using a 51-gene panel with histopathological assessment. Materials and Methods: Bone marrow samples from 96 consecutive patients evaluated for cytopenia were retrospectively analyzed for genetic alterations. Results: In the overall cohort (n = 96), the median follow-up was 8.1 months (range, 1\u201320). A total of 37 (39%) out of 96 patients were diagnosed with idiopathic cytopenia of undetermined significance (ICUS), 9 (9%) with clonal cytopenia of undetermined significance (CCUS), 9 (9%) with clonal cytopenia and monocytosis of undetermined significance (CCMUS), 34 (36%) with myelodysplastic syndrome (MDS), and 7 (7%) with myelodysplastic\/myeloproliferative neoplasm (MDS\/MPN). Among 41 patients in whom no cytogenetic abnormalities were detected by fluorescence in situ hybridization (FISH), somatic variants were identified by NGS. In CCUS, 88% of patients had a single variant, most commonly ASXL1 (44%), followed by TET2 (22%). In CCMUS, ASXL1 and DNMT3A (each 25%) were the most frequent variants. The mean variant allele frequency (VAF) was higher in MDS (33.4%) than in CCUS\/CCMUS (13.6%). In MDS patients aged 60 years and older, a higher number of variants were found compared to patients aged less than 60 years (p = 0.028). RUNX1 variants (n = 8) were associated with leukopenia (p = 0.012). Patients with SRSF2 variants (n = 4) had significantly poorer progression-free survival (p = 0.001). EZH2 and SETBP1 variants were associated with inferior overall survival (p = 0.04 and p = 0.019, respectively). In MDS patients (n = 34), thrombocytopenia (plt &lt; 100.000) was associated with shorter PFS (p = 0.005). Conclusions: Given that pre-MDS conditions are considered predictors of hematologic malignancies, conventional diagnostic workup may be insufficient to accurately identify these entities, whereas NGS provides significant additional diagnostic value.<\/jats:p>","DOI":"10.3390\/medicina62050868","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T10:15:27Z","timestamp":1777630527000},"page":"868","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Is Unidentified Cytopenia Truly Unidentified? Or Are We Overlooking Clonality?"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8551-868X","authenticated-orcid":false,"given":"Elcin","family":"Erdogan Yucel","sequence":"first","affiliation":[{"name":"Department of Hematology, Izmir City Hospital, University of Health Sciences,  Izmir 35535, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hale","family":"Bulbul Dilmen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Izmir City Hospital, University of Health Sciences,  Izmir 35535, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ozge","family":"Ozer Kaya","sequence":"additional","affiliation":[{"name":"Genetic Diagnosis Center, University of Health Sciences, Izmir City Hospital, Izmir 35540, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zehra","family":"Narli Ozdemir","sequence":"additional","affiliation":[{"name":"Department of Hematology, Izmir City Hospital, University of Health Sciences,  Izmir 35535, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Merve","family":"Kakci","sequence":"additional","affiliation":[{"name":"Department of Hematology, Dokuz Eylul University, Izmir 35210, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bahriye","family":"Celik","sequence":"additional","affiliation":[{"name":"Department of Hematology, Izmir City Hospital, University of Health Sciences,  Izmir 35535, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mustafa Kemal","family":"Yeniay","sequence":"additional","affiliation":[{"name":"Department of Hematology, Izmir City Hospital, University of Health Sciences,  Izmir 35535, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatma","family":"Keklik Karadag","sequence":"additional","affiliation":[{"name":"Department of Hematology, Ege University, Izmir 35040, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aybuke","family":"Olgun","sequence":"additional","affiliation":[{"name":"Department of Hematology, Izmir City Hospital, University of Health Sciences,  Izmir 35535, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4870-6945","authenticated-orcid":false,"given":"Taha Resid","family":"Ozdemir","sequence":"additional","affiliation":[{"name":"Genetic Diagnosis Center, University of Health Sciences, Izmir City Hospital, Izmir 35540, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cengiz","family":"Ceylan","sequence":"additional","affiliation":[{"name":"Department of Hematology, Izmir City Hospital, University of Health Sciences,  Izmir 35535, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oktay","family":"Bilgir","sequence":"additional","affiliation":[{"name":"Department of Hematology, Izmir City Hospital, University of Health Sciences,  Izmir 35535, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u0130nci","family":"Alacac\u0131o\u011flu","sequence":"additional","affiliation":[{"name":"Department of Hematology, Dokuz Eylul University, Izmir 35210, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alpert, N., Rapp, J.L., Mascarenhas, J., Scigliano, E., Tremblay, D., Marcellino, B.K., and Taioli, E. 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