RESUMO
PURPOSE: Chronic neutrophilic leukemia is a rare form of myeloproliferative neoplasm characterized by mature neutrophil hyperleukocytosis. The majority of patients harbor somatic mutations of CSF3R gene and are potentially amenable to targeted therapy with JAK inhibitors. The incidence and clinical significance of additional mutations requires clarification. MATERIALS AND METHODS: A next-generation sequencing approach for myeloid malignancy-associated mutations was applied to diagnostic and matched blast crisis samples from four chronic neutrophilic leukemia patients. RESULTS: Next-generation sequencing confirmed the CSF3R T618I in all patients with identification of concurrent SRSF2, SETBP1, NRAS and CBL mutations at diagnosis. At blast crisis, clonal evolution was evidenced by an increased CSF3R T618I allele frequency and by loss or acquisition of CBL and NRAS mutations. CONCLUSION: The diagnostic utility of a targeted next-generation sequencing approach was clearly demonstrated with the identification of additional mutations providing the potential for therapeutic stratification of chronic neutrophilic leukemia patients.
Assuntos
Crise Blástica/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Leucemia Neutrofílica Crônica/genética , Leucemia Neutrofílica Crônica/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , MutaçãoRESUMO
Se describe un caso de leucemia neutrofílica crónica asociada a leucemia de piel, en una paciente de 49 años de edad, sexo femenino, diagnosticada en julio de 2001; con presencia de 43.605/mm3 neutrófilos en sangre periférica y médula ósea hipercelular con serie granulocítica hiperplástica. el estudio histopatológico de la piel reveló infiltrado del 70 porciento de blastos tipo mieloide. Fue tratada con hidroxiurea, siendo favorable la resuesta clínica y laboratorial. el hemograma de diciembre de 2001 presentó 5.656/mm3 neutrófilos.