title: 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.
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Hematology, Central South University Xiangya Hospital, Changsha, China.
authors: Jie
authors: J
authors: Peng
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Zhuang
authors: Z
authors: Zuo
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Hematology, Central South University Xiangya Hospital, Changsha, China.
authors: Bin
authors: B
authors: Fu
authors: Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Yasuhiro
authors: Y
authors: Oki
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Guilin
authors: G
authors: Tang
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Maitrayee
authors: M
authors: Goswami
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Priyanka
authors: P
authors: Priyanka
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Tariq
authors: T
authors: Muzzafar
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: L Jeffrey
authors: LJ
authors: Medeiros
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Rajyalakshmi
authors: R
authors: Luthra
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Sa A
authors: SA
authors: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D000090243:Nucleophosmin; D012189:Retrospective Studies
chemical_list: C000716967:NPM1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000090243:Nucleophosmin
keywords: acute myeloid leukemia; chronic myelomonocytic leukemia; karyotype; mutation; nucleophosmin 1