Navegando por Palavras-chave "gene npm1"

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    Estudo da mutação do gene npm1 e sua relação com a mutação do gene flt3 em pacientes adultos com leucemia mieloide aguda
    (Universidade Federal de São Paulo (UNIFESP), 2014-11-26) Kimura, Eliza Yuriko Sugano [UNIFESP]; Yamamoto, Mihoko Yamamoto [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Introduction: AML is an aggressive and highly heterogeneous hematologic malignancy, as well as the most prevalent acute leukemia in adults. NPM1 mutation is a largely observed molecular change with significant prognostic value, especially in the intermediate cytogenetic group. Objective: Evaluate the frequency of NPM1 mutation, its prognostic value through clinical and laboratorial factors comparison and its association to FLT3 mutation. Methods: 121 consecutive patients with de novo AML were analyzed. The median age was 55 years (57 men and 64 women aged between 17-88). Diagnostic methods included morphological analysis, flow cytometric immunophenotyping and conventional G banding cytogenetic analysis. NPM1 molecular study was performed by sequencing the exon 12 genomic DNA, previously purified and subjected to PCR. The chain termination method applied was dideoxynucleotides and the amplification was reverse primer based. The electropherograms were analyzed by ABI PRISM 377 DNA Sequencing Analysis version 3.3. The sequences were aligned to the standard sequence contained in the GenBank database (accession number NM_002520.5). Results: The distribution of patients according to FAB classification were: 12 M0, 23 M1, 37 M2, 20 M3, 12 M4, M5a 6, 7 M5b, 2 M6, 1 N / C and 1 basophil. The NPM1 mutation was detected in 19.8% of LMAs studied and in 27.3% of the cytogenetic intermediate risk group. TCTC duplication (mutation A) was the most frequent, accounting for 77.3%. The NPM1 mutation was associated with increased leukocytosis (p = 0.002) and a higher percentage of blast cells in BM (p = 0.016). It was more frequent in monocytic LMAs (p = 0.003) and was rare or absent in M3 and M0. The CD34 expression was inversely related to the presence of the mutation and the double negative CD34 / HLA-DR (p <0.001 and p <0.012, respectively). CD14 expression was associated with NPM1 mutation (p = 0.022). In cytogenetic intermediate risk group, all parameters kept association and lower CD117 expression was observed in AML NPM1-mut compared to NPM1wt (63.5 vs. 96.5; p = 0.048). Assessing the molecular favorable prognosis group (NPM1-mut / FLT3wt) and the adverse group (NPM1wt / FLT3-ITD), the lack of expression of CD34 and double-negative for CD34 and HLA DR (p <0.001 and p = 0.005, respectively) were both associated with the favorable group. Age, gender and WBC showed no relevance. Furthermore, 18.2% (6/33) presented the favorable genetic prognosis (NPM1-mut / FLT3wt) while 9.1% (3/33) the adverse prognosis (NPM1wt / FLT3-ITD). Conclusion: The co-evaluation of FLT3 and NPM1 mutations enabled reallocation of 27% of the cytogenetic intermediate risk group patients between favorable or adverse prognosis group.