Molecular and cytogenetic abnormalities in acute myeloid leukemia: review and case studies

Abstract

Objective: To study the frequency of mutations that may lead to a good or bad prognosis, as well as their relation with the karyotype and immunophenotype in patients with acute myeloid leukemia. Methods: Thirty samples of patients with acute myeloid leukemia were studied, in which FLT3-ITD, FLT3-TKD and NPM1 mutations were investigated. All samples were submitted to immunophenotyping and 25 to karyotyping. results: An occurrence of 33.3% NPM1 mutation and an equal number of FLT3-ITD mutation were observed. When only the cases with normal karyotype were studied, this figures increased to 50 and 40%, respectively. Eight percent of cases with normal karyotype and genotype NPM1+/FLT3-were included in the group of acute myeloid leukemia with good prognosis. The typical phenotype of acute myeloid leukemia with normal karyotype and mutated NPM1 (HLA-DR and CD34 negative) was not observed in this small series. conclusion: Good prognosis cases were identified in this series, emphasizing the need to include new genetic markers in the diagnostic routine for the correct classification of acute myeloid leukemia, to more properly estimate prognosis and determine treatment. Não observamos o fenótipo típico das leucemias mieloides agudas com cariótipo normal e NPM1 mutado (HLA-DR e CD34 negativos) nesta pequena casuística. conclusão: O presente estudo foi capaz de identificar casos de bom prognóstico, enfatizando que há necessidade de se incorporarem à rotina diagnóstica novos marcadores genéticos, para a correta estratificação prognóstica e orientação terapêutica das leucemia mieloide aguda. Keywords

Detecção de mutações no gene KIT em leucemia mieloide aguda

“…Several of the patients in this study had been assessed in a previous study for mutations in their FLT3 and NPM1 genes (15) . None of the patients with these mutations showed concomitant mutation in the KIT gene.…”

The possible significance of trisomy 8 in acute myeloid leukemia

“…4 However, the cytogenetic study is important to confirm the wide variety of common, rare, novel chromosomal translocations in patients with haematopoietic disorders which provide valuable diagnostic and prognostic information. 5 In fact, patients with trisomy 8 had a shorter survival which significantly increased the risk for leukemic transformation than patients with other chromosomal rearrangements. Thus, the karyotype of leukemic blast has been shown prognostic determinants for AML.…”

Role of Cytogenetic Evaluation in Diagnosis of Acute Myeloid Leukemia

“…Thus, the complete diagnostic and prognostic testing of bone marrow is important to predict the outcomes and post induction treatments [5]". Thus, the cytogenetic study is important to confirm the wide variety of common, rare and novel chromosomal anomalies in patients with haematopoietic disorders may provide valuable diagnostic and prognostic information [6]".…”

“…Ahmad et al [7]" showed that the t (8; 21) (q22; q22) is most common recurrent chromosomal translocation seen in nearly 10-15% of AML-M2 subtype. While t(15; 17) (q22; q12) found in only 5% of the specific type of AML such as Acute Promyelocytic Leukaemia(APL) and inv(16) (p13q22) found in approximately 8% of AML Velloso et al [6]" have reported that the 50-60% of patients shown intermediate risk group with chromosomal constitution as t(9; 11),+8,-Y with normal karyotype, while 25-30% patients shown poor risk group with MLL, t(6; 9), monosomy and deletion of chromosome 5 and 3, inv(3) and 25% of patients belong to good risk group with cytogenetic chromosomal constitution as t(15; 17) (q22; q12), t(8; 21) (q22; q22) and inv (16) (p13; q22).…”