Impact of Variants in the ATIC and ARID5B Genes on Therapeutic Failure with Imatinib in Patients with Chronic Myeloid Leukemia.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm derived from the balanced reciprocal translocation of chromosomes 9 and 22 t (9q34 and 22q11), which leads to the formation of the Philadelphia chromosome and fusion of the BCR-ABL genes. The first-line treatment for CML is imatinib, a tyrosine kinase inhibitor that acts on the BCR-ABL protein. However, even though it is a target-specific drug, about 25% of patients do not respond to this treatment. The resistance mechanisms involved in this process have been investigated and studies have shown that germinal alterations can influence this mechanism. The aim of this work was to investigate 32 polymorphisms in 24 genes of carcinogenic pathway to verify the influence of these genetic variants on the response to treatment with imatinib. Our results demonstrated that individuals with the recessive GG genotype for the rs2372536 variant in the ATIC gene are approximately three times more likely to experience treatment failure with imatinib (p = 0.045, HR = 2.726, 95% CI = 0.9986-7.441), as well as individuals with the TT genotype for the rs10821936 variant in the ARID5B gene, who also have a higher risk for treatment failure with imatinib over time (p = 0.02, HR = 0.4053, IC 95% = 0.1802-0.911). In conclusion, we show that variants in the ATIC and ARIDB5 gene, never screened in previous studies, could potentially influence the therapeutic response to imatinib in patients treated for CML.

Influence of late treatment on how chronic myeloid leukemia responds to imatinib.

INTRODUCTION: In Brazil, patients with chronic myeloid leukemia (CML) in the chronic phase were not given first-line imatinib treatment until 2008. Therefore, there was a long period of time between diagnosis and the initiation of imatinib therapy for many patients. This study aims to compare the major molecular remission (MMR) rates of early versus late imatinib therapy in chronic phase CML patients. METHODS: Between May 2002 and November 2007, 44 patients with chronic phase CML were treated with second-line imatinib therapy at the Hematology Unit of the Ophir Loyola Hospital (Belém, Pará, Brazil). BCR-ABL transcript levels were measured at approximately six-month intervals using quantitative polymerase chain reaction. RESULTS: The early treatment group presented a 60% probability of achieving MMR, while the probability for those patients who received late treatment was 40%. The probability of either not achieving MMR within one year of the initiation of imatinib therapy or losing MMR was higher in patients who received late treatment (79%), compared with patients who received early treatment (21%, odds ratio=5.75, P=0.012). The probability of maintaining MMR at 30 months of treatment was 80% in the early treatment group and 44% in the late treatment group (P=0.0005). CONCLUSIONS: For CML patients in the chronic phase who were treated with second-line imatinib therapy, the probability of achieving and maintaining MMR was higher in patients who received early treatment compared with those patients for whom the time interval between diagnosis and initiation of imatinib therapy was longer than one year.

Influence of late treatment on how chronic myeloid leukemia responds to imatinib

INTRODUCTION: In Brazil, patients with chronic myeloid leukemia (CML) in the chronic phase were not given first-line imatinib treatment until 2008. Therefore, there was a long period of time between diagnosis and the initiation of imatinib therapy for many patients. This study aims to compare the major molecular remission (MMR) rates of early versus late imatinib therapy in chronic phase CML patients. METHODS: Between May 2002 and November 2007, 44 patients with chronic phase CML were treated with second-line imatinib therapy at the Hematology Unit of the Ophir Loyola Hospital (Belém, Pará, Brazil). BCR-ABL transcript levels were measured at approximately six-month intervals using quantitative polymerase chain reaction. RESULTS: The early treatment group presented a 60 percent probability of achieving MMR, while the probability for those patients who received late treatment was 40 percent. The probability of either not achieving MMR within one year of the initiation of imatinib therapy or losing MMR was higher in patients who received late treatment (79 percent), compared with patients who received early treatment (21 percent, odds ratio=5.75, P=0.012). The probability of maintaining MMR at 30 months of treatment was 80 percent in the early treatment group and 44 percent in the late treatment group (P=0.0005). CONCLUSIONS: For CML patients in the chronic phase who were treated with second-line imatinib therapy, the probability of achieving and maintaining MMR was higher in patients who received early treatment compared with those patients for whom the time interval between diagnosis and initiation of imatinib therapy was longer than one year.

Differential molecular response of the transcripts B2A2 and B3A2 to imatinib mesylate in chronic myeloid leukemia.

Chronic myeloid leukemia (CML) originates from the hematopoietic stem cell and is characterized by the reciprocal translocation t(9;22)(q34;q11), which results in the BCR-ABL fusion gene on chromosome 22q-, also known as the Philadelphia chromosome. This chimeric gene codes for a cytoplasmic protein with constitutive tyrosine-kinase activity, responsible for cellular transformation and leukemogenesis in CML. The aim of this observational cohort study was to discriminate and quantify BCR-ABL transcripts in the peripheral blood of patients with CML who were treated with imatinib mesylate (Glivec, Novartis). Twenty-two patients were followed for six months during treatment. Quantitative real time polymerase chain reaction was performed before treatment and after 3 and 6 months from treatment initiation. As compared with the third month, there was a significant decrease in BCR-ABL expression in the sixth month of treatment (P = 0.0002). At the sixth month, there was a significant difference in the levels of the two major transcripts of BCR-ABL, B2A2 and B3A2 (P = 0.0347), indicating that B2A2 may be more sensitive to imatinib. The results of our study indicate that imatinib is able to modify the natural history of CML, and raise the hypothesis that patients who express the B2A2 transcript may have a better prognosis.

Perfil nutricional da criança que "não come" (queixa materna) / Nutritional profile of children who

A disciplina de nutrição e metabolismo da Universidade Federal de São Paulo, vem desenvolvendo um programa de atendimento ambulatorial de crianças com queixa materna de que não comem, de onde se originou deste trabalho que tem como objetivo avaliar o perfil nutricional, a dinâmica alimentar e a existência de possíveis conflitos psicológicos envolvidos na queixa alimentar destas criança. Foram estudadas 68 crianças, 37 de sexo masculino e 31 do sexo feminino entre as idades de 1 a 12 anos. As consultas constaram de investigação pediátrica, nutricional e psicológica. Estas avaliações foram realizadas através de anamneses específicas, medidas antropométricas, inquéritos nutricionais, observação direta da mãe-criança e testes de desenho (House-Tree-Person. A maior incidência da queixa foi na faixa etária de 1 a 3 anos. As infecções respiratórias foram as doenças mais freqüentes associadas à queixa. Houve relação significante entre o estado nutricional e a presença de patologia. De acordo com a curva e escores Z, 58 crianças estavam Eutróficas. A maioria das crianças teve a adequação da ingestão energética e de nutrientes abaixo de 80% das recomendações, sendo que a ingestão protéica ficou acima de 100% em 64 crianças. A rotina e o esquema alimentar se mostraram inadequadas. Grande parte das crianças (80,9%) e das mães apresentaram algum tipo de transtorno psicológico. Foi encontrado anorexia verdadeira em 10 crianças (14,7%) e anorexia comportamental em 58 crianças (85,3%).

Deficiência do crescimento: características antropométricas de crianças, e de seus pais, em atendimento ambulatorial / Growth disorder: antropometry of the children and your mother and father

Os autores descrevem os resultados da avaliaçäo de 316 crianças referidas ao Ambulatório de Baixa Estatura do Departamento de Pediatria da Escola Paulista de Medicina, sendo 235 (74,4 por cento) de Baixa Estatura (BE) e 81 (25,6 por cento) em Zona de Vigilância do Crescimento(ZV). Estas crianças foram analisadas segundo a idade, faixa etária, sensibilizaçäo, antopometria ao nascimento e dos pais. Notaram-se 30,9 (por cento) de Baixo Peso (BP) e 37,2 (por cento) de Peso Inadequado (PI) ao nascimento, entre as crianças de BE. Nos casos em ZV, 23,8 (por cento) eram de BP e 38,1 (por cento) de PI. Com relaçäo ao comprimento de nascimento notou-se que, nos casos de BE, 62,1 (por cento) eram menores de 48,5 cm e, entre aquelas em ZV, 52,8 (por cento) também apresentavam comprimento menor que 48,5 cm, que, comparadas à antropometria do recém-nascido brasileiro, apresentavam diferenças significantes. A antropometria dos pais destas crianças mostra características específicas, de modo que, associada à de nascimento, pode ser considerada como fator de risco para a BE, principalmente nos casos diagnosticados como de causa familiar e/ou constitucional