AUTHOR=Xicoy Blanca , Pomares Helena , Morgades Mireia , Germing Ulrich , Arnan Montserrat , Tormo Mar , Palomo Laura , Orna Elisa , Della Porta Matteo , Schulz Felicitas , Díaz-Beya Marina , Esteban Ada , Molero Antonieta , Lanino Luca , Avendaño Alejandro , Hernández Francisca , Roldan Verónica , Ubezio Marta , Pineda Alberto , Díez-Campelo María , Zamora Lurdes 

TITLE=Chronic myelomonocytic leukemia with ring sideroblasts/SF3B1 mutation presents with low monocyte count and resembles myelodysplastic syndromes with-RS/SF3B1 mutation in terms of phenotype and prognosis

JOURNAL=Frontiers in Oncology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1385987

DOI=10.3389/fonc.2024.1385987

ISSN=2234-943X

ABSTRACT=<sec><title>Introduction</title><p>Chronic myelomonocytic leukemia (CMML) and myelodysplastic syndromes (MDS) with ring sideroblasts (RS) or <italic>SF3B1</italic> mutation (MDS-RS/<italic>SF3B1</italic>) differ in many clinical features, but share others, such as anemia. RS and <italic>SF3B1</italic> mutation can also be found in CMML.</p></sec><sec><title>Methods</title><p>We compared CMML with and without RS/<italic>SF3B1</italic> and MDS-RS/<italic>SF3B1</italic> considering the criteria established by the 2022 World Health Organization classification.</p></sec><sec><title>Results</title><p>A total of 815 patients were included (CMML, n=319, CMML-RS/<italic>SF3B1</italic>, n=172 and MDS-RS/<italic>SF3B1</italic>, n=324). The percentage of RS was ≥15% in almost all CMML-RS/<italic>SF3B1</italic> patients (169, 98.3%) and most (125, 72.7%) showed peripheral blood monocyte counts between 0.5 and 0.9 x10<sup>9</sup>/L and low risk prognostic categories. CMML-RS/<italic>SF3B1</italic> differed significantly from classical CMML in the main clinical characteristics, whereas it resembled MDS-RS/<italic>SF3B1</italic>. At a molecular level, CMML and CMML-RS/<italic>SF3B1</italic> had a significantly higher frequency of mutations in <italic>TET2</italic> (mostly multi-hit) and <italic>ASXL1</italic> (p=0.013) and CMML had a significantly lower frequency of <italic>DNMT3A</italic> and <italic>SF3B1</italic> mutations compared to CMML/MDS-RS/<italic>SF3B1</italic>. Differences in the median overall survival among the three groups were statistically significant: 6.75 years (95% confidence interval [CI] 5.41-8.09) for CMML-RS/<italic>SF3B1</italic> vs. 3.17 years (95% CI 2.56-3.79) for CMML vs. 16.47 years (NA) for MDS-RS/<italic>SF3B1</italic>, p&lt;0.001. Regarding patients with CMML and MDS, both with <italic>SF3B1</italic> mutation, survival did not significantly differ. CMML had a higher risk of transformation to acute myeloid leukemia (24% at 8 years, 95%CI 19%-30%).</p></sec><sec><title>Discussion</title><p>CMML-RS/<italic>SF3B1</italic> mutation resembles MDS-RS/<italic>SF3B1</italic> in terms of phenotype and clearly differs from CMML. The presence of ≥15% RS and/or <italic>SF3B1</italic> in CMML is associated with a low monocyte count. <italic>SF3B1</italic> mutation clearly improves the prognosis of CMML.</p></sec>