Chronic myelomonocytic leukemia with nucleophosmin (NPM1) mutation

Abstract

Nucleophosmin (NPM1) mutations in chronic myelomonocytic leukemia (CMML) are extremely uncommon, and the clinicopathologic features of these neoplasms are poorly characterized. Over a 10-yr interval, NPM1 mutation analysis was performed in 152 CMML at our institution. NPM1 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. NPM1 mutation allele burden was <5% in two patients and >10% in six patients. Four (50%) patients, all with >10% NPM1, progressed AML with a median interval of 11 months (range, 1-21). Compared with 144 CMML without NPM1 mutations, CMML patients with NPM1 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), TET2(2/5), ASXL1(1/5,) and FLT3(0/8) were not significantly different between these two groups. In summary, CMML with NPM1 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.

Acquired expression of CblQ367P in mice induces dysplastic myelopoiesis mimicking chronic myelomonocytic leukemia

“…4,6 Investigation of the mechanisms underlying the disease progression has identified genetic alterations, such as mutations in the Asxl1 (additional sex combslike 1), Setbp1 (SET-binding protein 1), and NPM1 (nucleophosmin) genes [43][44][45][46] ; however, little is known about genes whose expressional changes are responsible for disease evolution. By employing retrovirusmediated mutagenesis, we identified Evi1, a gene encoding a transcription factor involved in normal hematopoiesis and leukemogenesis, 28 as a cooperative gene with Cbl Q367P and demonstrated that overexpressed EVI1 synergized with CBL Q367P to develop AML.…”

How I investigate chronic myelomonocytic leukemia

“…Such cases show the characteristic morphologic features of CMML, but higher WBC and more severe anemia. They show increased tendency for AML progression and poorer prognosis so that a more aggressive clinical intervention may be indicated …”

Nucleophosmin 1 (NPM1) mutations in chronic myelomonocytic leukemia and their prognostic relevance

“…[8] NPM1 mutations are infrequent in CMML (<5%) and MDS (<5%) and have an unclear prognostic impact. [9-11] We carried out this study to assess the i) frequency and clinical correlates, ii) prognostic impact and iii) survival outcomes related to NPM1 mutations in CMML.…”