Caracterização imunomolecular das leucemias linfoides agudas tipo B (LLA-B) em crianças no estado do Maranhão e associação entre parâmetros clínico-laboratoriais a resposta ao tratamento nas LLA ETV6-RUNX1 positivas

Abstract

Introduction: Acute lymphoid leukemias (ALL) constitute 25% of cases of pediatric cancers and are divided into T-ALL and B-ALL, the latter being the most frequent subtype. The B-ALL is classified by the presence of fusion genes, highlighting ETV6-RUNX1 (E / R) due to its presence in 25% of cases of B-ALL and its association with an uncertain prognosis. This study aimed to characterize the B-ALL in the State of Maranhão, as well as to associate immunomolecular and biochemical parameters with the prognosis of patients with ALL-B E/R positive. Material and methods: Thirty four patients from the reference center of the state of Maranhão had clinical, morphological, laboratory and immunophenotypic data recorded in a database for later association. After molecular characterization by PCR, the patients were stratified by the presence or absence of the fusion genes MLL-AF4, BCR-ABL (p190), E/R and TCF3-PBX1. In the positive group for the E/R gene, the association between prognosis with immunophenotypic and biochemical data was made, having as a comparison group negative ETV6-RUNX1 patients, without excluding the absence of other fusion genes. Results: Of the 34 patients initially studied, 29 were classified as B-ALL and 5 as T-ALL. The frequency of fusion genes in patients with B-ALL was 38% (n = 11) E/R, 21% (n = 6) TCF3-PBX1 and 41% (n = 12) negative for the fusion genes studied. The mean age of the positive E / R patients was 3.7 ± 3.4 years whereas in the negative patients it was 4.9 ± 3.5 years. The subtypes of ALL-B E/R found were common B-ALL in 72.7% (n = 8) and 27.3% (n = 3) of pre-B ALL. Among the biochemical parameters analyzed, there was no difference between the analyzed groups. In relation to the aberrant and / or fusion-immunofenotypic markers analyzed in both groups, there was no difference, however the CD56 and CD9 markers were expressed among the E/R patients. Regarding the prognosis of the E/R patients during the evaluation of response to treatment, it was observed that 3 of the 5 CD9 + patients and 2 of the 3 CD56 + patients had poor responses at some of the treatment response checkpoints. In addition, 27.3% (n = 3) of the cases evolved to death and of these 2 expressed CD9 and 1 expressed CD56. Conclusion: According to the results, we performed for the first time the characterization of the recurrent molecular alterations of B-ALL in the State of Maranhão and we observed that patients positive for the E/R fusion gene can present a clinical outcome variable according to the immunophenotypic profiles.