Caso atípico de leucemia mieloide aguda con coexistencia de NPM1-A e inversión del cromosoma 16 / A rare case of acute myeloid leukemia with coexistence of NPM1-A mutation and chromosome 16 inversion

Introducción: La leucemia mieloide aguda (LMA) es un grupo heterogéneo de desórdenes clonales con una gran variabilidad en términos de patogénesis, características morfológicas, genéticas e inmunofenotípicas. Las mutaciones en el gen NPM1 representan una de las más comunes en las LMA y está asociada con una respuesta clínica favorable. Por citogenética, la inversión del cromosoma 16 define el subgrupo de las LMA de factor de unión al grupo con un pronóstico favorable. Objetivo: Describir un caso con diagnóstico de LMA en los cuales el estudio molecular del gen NPM1 y de la inv(16) fueron positivos. Caso clínico: A nivel molecular, la hibridación in situ fluorescente fue positivo a la inv(16) y por biología molecular fue positivo tanto a la inv(16) como al gen NPM1-A, elementos de baja frecuencia de aparición. Se le administró a la paciente un esquema de poliquimioterapia no intensiva para mejorarla clínicamente. Después de una mejoría clínica inicial, la paciente comenzó con complicaciones y falleció. Conclusiones: La coexistencia de estas dos mutaciones es muy poco frecuente en pacientes con LMA, y a pesar de ser de buen pronóstico la paciente falleció a los pocos días de tratamiento(AU)

Introduction: Acute myeloid leukemia (AML) is a heterogeneous group of clonal disorders with great variability in terms of pathogenesis, morphological, genetic and immunophenotypic characteristics. NPM1 mutations represent one of the most common in AML and are associated with favorable clinical response. By cytogenetics, chromosome 16 inversion defines, with a favorable prognosis, the core‐binding factor for the subgroup of AMLs Objective: To describe a AML case in which the molecular study of the NPM1 gene and the chromosome 16 inversion were positive. Clinical case: At the molecular level, fluorescent in situ hybridization was positive for chromosome 16 inversion and, by molecular biology, it was positive for both chromosome 16 inversion and for the NPM1-A gene, elements with a low frequency of appearance. The patient was administered a non-intensive combination as part of a chemotherapy regimen to improve her clinical status. After initial clinical improvement, the patient began with complications and died. Conclusions: The coexistence of these two mutations is very rare in patients with AML. Despite presenting a good prognosis, the patient died after a few days of treatment(AU)

NPM1 mutation in acute myeloid leukemia with normal karyotype：a clinical analysis / 白血病·淋巴瘤

Objective To investigate the frequency of NPM1 mutation and its clinical significance in patients with cytogenetically normal acute myeloid leukemia (CN-AML). Methods The data of 190 patients with CN-AML were collected from Department of Hematology, Tongji Hospital between January 2008 and June 2015, and the discrepancies in clinical features and efficacy between CN-AML patients with NPM1 mutation and those without NPM1 mutation were also analyzed. Results Among the 190 CN-AML patients, NPM1 mutation was found in 44 patients (23.16 %). The proportion of bone marrow blast cells and the count of peripheral white blood cells in patients with NPM1 mutation were higher than those in patients without NPM1 mutation (75.82 % vs. 63.87 % , P <0.05; 75.7 ×109/L vs. 60.0 ×109/L, P <0.05). The rate of response (complete remission + partial remission) in patients with NPM1 mutation was also higher than that in patients without NPM1 mutation [70.09 %(22/31) vs. 56.91 %(45/79), P<0.05) ]. Conclusion NPM1 mutation is associated with higher tumor burden and higher remission rate in CN-AML patients.

Clinical study of adult acute myeloid leukemia with nucleophosmin cytoplastic positive / 白血病·淋巴瘤

Objective To evaluate the clinical feature of adult acute myeloid leukemia with nucleophosmin (NPM1) cytoplastic positive (NPMc+AML), and to investigate the significance of the NPM1 gene mutations regularly in detecting the early relapse. Methods The NPM1 gene mutations was screened by the PCR-capillary electrophoresis in 95 newly diagnosed adult AML patients. 5 complete remission AML patients were selected to detecte the NPM1 gene mutations regularly. Results In 95 cases of adult AML patients, the incidence of the NPM1 mutations was 9.5 % (28/95). The incidence of the NPM1 mutations in patients (≥40-year-old) was higher clearly than it' s in pazients (40-year-old) (λ 2= 6.963, P = 0.012). That in the AML patients with normal karyotype (51.1%) was higher than that in the patients with abnormal karyotype (8.3 %) (λ2= 20.860, P= 0.0000). NPM1 mutations occured with a considerate percentage in AML patients with M5/M2 subtype. In AML with recurrent genetic abnormalities the NPM1 mutations wasn' t found.The white blood cell count, platelet count, lactate dehydrogenase in the NPMc+AML patients were clearly higher than that in the NPMc-AML patients (t were individually 4.132, 4.603, 4.069, P ＜0.05). The rate of complete remission, relapse-free survival and overall survival in the NPMc+AML patients were also higher than that in the N PMc-AML patients (λ 2 were individually 10.448, 4.146, 4.384, P ＜0.05). In cases detected regularly NPM1 mutations preceded the hematological relapse about 1.5-2 months. Conclusion NPM1 gene mutations has a higher incidence in adult AML, particularly in normal karyotype AML. The clinical manifestations are older, and higher in white blood cell count, platelet count, and lactate dehydrogenase. The NPM1 mutations in adult AML is a good factor for prognosis. The regular detection of NPM1 mutation could find relapse early.