Genetic mutations associated with blood count abnormalities in myeloid neoplasms

Myelodysplastic syndromes (MDS) predominantly present with varying degrees of cytopenia, while myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) exhibit proliferative features. Genetic defects underlying different complete blood count (CBC) alterations remain to be defined. We aimed to evaluate mutations and impacts on abnormal blood counts in MDS and MDS/MPN. MDS and MDS/MPN patients were recruited and sequenced by targeted next-generation sequencing. Clinical parameters, especially CBC, were evaluated for the association with genetic abnormalities and clinical outcomes. A total of 168 patients with myeloid neoplasms were recruited (92 cases of low-risk MDS, 57 cases of high-risk MDS and 19 cases of MDS/MPN). Compared to low-risk MDS and MDS/MPN, patients with high-risk MDS were presented with more severe neutropenia with 17.5% showing absolute neutrophil counts (ANC) lower than 0.5 × 10⁹/L. Patients with MDS/MPN more commonly harboured mutations and had a higher number of mutations per case than low-risk MDS (94.7% vs. 56.5%; <i>p</i> &lt; 0.001 and 3 vs. 1; <i>p</i> &lt; 0.001, respectively). Patients with <i>SF3B1</i> mutations showed lower haemoglobin levels than wild-type (7.9 vs. 8.4 g/dL, <i>p</i> = 0.02), but were associated with normal platelet counts (286 vs. 93 × 10⁹/L; <i>p</i> &lt; 0.001). Patients with <i>U2AF1</i> mutations were associated with more severe leukopenia than wild-type (3 vs. 4.18 × 10⁹/L; <i>p</i> = 0.02). <i>KRAS</i> mutations were associated with monocytosis (<i>p</i> &lt; 0.001). Multivariate analysis revealed high-risk MDS, MDS/MPN, severe neutropenia (ANC &lt; 0.5 × 10⁹/L), and mutations in <i>ASXL1</i> and <i>SETBP1</i> were associated with inferior survival outcomes. Certain mutations were related to more severe anaemia, lower white blood cell count or monocytosis in Asian MDS and MDS/MPN patients.