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.

骨髓增生异常综合征（Myelodysplastic syndromes, MDS）主要表现为不同程度的血细胞减少症，而骨髓增生异常综合征/骨髓增殖性肿瘤（MDS/MPN）则呈现增殖性特征。目前，不同全血细胞计数（complete blood count, CBC）异常背后的遗传学缺陷仍有待阐明。本研究旨在评估MDS及MDS/MPN患者的基因突变情况及其对异常血细胞计数的影响。本研究招募了MDS和MDS/MPN患者，并通过靶向二代测序进行测序检测。同时对临床参数（尤其是全血细胞计数）与遗传学异常及临床结局的相关性进行了评估。本研究共纳入168例髓系肿瘤患者，其中低危MDS 92例、高危MDS 57例、MDS/MPN 19例。与低危MDS及MDS/MPN患者相比，高危MDS患者的中性粒细胞减少更为严重，17.5%的患者中性粒细胞绝对计数（absolute neutrophil counts, ANC）低于0.5×10⁹/L。MDS/MPN患者的基因突变检出率更高，且每例患者的平均基因突变数更多，分别为94.7% vs. 56.5%（p<0.001）以及3个vs. 1个（p<0.001）。携带SF3B1基因突变的患者血红蛋白水平低于野生型患者（7.9 vs. 8.4 g/dL，p=0.02），但血小板计数多处于正常范围（286 vs. 93×10⁹/L；p<0.001）。携带U2AF1基因突变的患者白细胞减少程度较野生型患者更为严重（3 vs. 4.18×10⁹/L；p=0.02）。KRAS基因突变与单核细胞增多症相关（p<0.001）。多因素分析显示，高危MDS、MDS/MPN、严重中性粒细胞减少（ANC<0.5×10⁹/L）以及ASXL1和SETBP1基因突变与不良生存结局相关。在亚洲MDS及MDS/MPN患者中，部分基因突变与更严重的贫血、更低的白细胞计数或单核细胞增多症相关。