Chronic myelomonocytic leukemia with nucleophosmin ( NPM 1 ) mutation

Nucleophosmin ( NPM 1 ) mutations in chronic myelomonocytic leukemia ( CMML ) are extremely uncommon, and the clinicopathologic features of these neoplasms are poorly characterized. Over a 10‐yr interval, NPM 1 mutation analysis was performed in 152 CMML at our institution. NPM 1 mutations were identified in 8 (5.3%) patients, five men and three women, with a median age of 72 yr (range, 27–87). In all patients, the bone marrow was hypercellular with multilineage dysplasia, monocytosis, and retained maturation supporting a diagnosis of CMML . NPM 1 mutation allele burden was <5% in two patients and >10% in six patients. Four (50%) patients, all with >10% NPM 1, progressed AML with a median interval of 11 months (range, 1–21). Compared with 144 CMML without NPM 1 mutations, CMML patients with NPM 1 mutation presented with more severe anemia ( P  =   0.053), higher BM monocyte percentage ( P  =   0.033), and an increased tendency for AML progression ( P  =   0.088) and an inferior overall survival ( P  =   0.076). Mutations involving NRAS / KRAS (2/7), TET 2(2/5), ASXL 1(1/5,) and FLT 3(0/8) were not significantly different between these two groups. In summary, CMML with NPM 1 mutation shows histopathological features of CMML , but patients appear to have a high probability for AML progression and may require aggressive clinical intervention, especially in patients with a high mutation burden.