Frequency of the BCR/ABL rearrangements and associated alterations detected by FISH during monitoring of patients taking imatinib mesylate in isolation

A introdução do mesilato de imatinibe como tratamento da leucemia mielóide crônica tem salvado muitos pacientes, mas o sucesso da terapia tem sido prejudicado pela resistência e possível não destruição do clone maligno. Este artigo descreve a resposta citogenética e padrões citogenéticos anormais envolvendo os genes ABL e BCR detectados por FISH em pacientes em uso exclusivo de imatinibe. Os resultados mostraram que outras alterações envolvendo os genes BCR e ABL não parecem estar relacionadas à resistência à droga, elas ocorrem em baixas freqüências e podem não estar associadas à resposta citogenética ou ao tempo de tratamento. Contudo, a resposta ao imatinibe parece ser individual e imprevisível, independente do tempo e do início do tratamento após o diagnóstico.

Estudo das alterações cariotípicas, do rearranjo gênico BCR/ABL e do cromossomo 20 em leucemias

Leukemia is a genetic disease from a noncontrolled abnormal process of the hematopoietic cells' differentiation and proliferation. Some alterations of structure and number of chromosomes have been well and specifically observed in leukemia. The detection of these alterations is highly significant in providing the patients' diagnosis, prognosis and treatment as well as the understanding of the genetic bases of this disease. The purpose of this work is to study some chromosomal alterations in peripheral blood and/or bone marrow in patients with different leukemia types by means of conventional cytogenetic techniques, and also to investigate the presence of BCR/ABL gene rearrangement and some alterations in chromosome 20 by the FISH technique. Samples of peripheral blood and/or bone marrow of 28 patients, who were not under chemoor radio-therapeutic treatment, were studied: 15 with CML, 11 with AML and 2 with ALL. The alteration most frequent was t(9;22) in the CML, whose presence or absence was related to a good or bad prognosis, respectively. A case of AMI showed inv(16)(p13q22), related to a good prognosis. Some alterations not reported previously in the literature were found, such as the trisomy in chromosome 2 associated to chromosome Ph showing some disease progress in one of the CML cases and t(5;16)(q13;q22) in an AML patient. One of the cases was submitted to an allogeneic hone marrow transplant. The monitoring after the 23 rd day of transplant, detected 95% of the donor cells suggesting the procedure had succeeded. Two patients, an AMI and the other ALL, showed trisomy of chromosome 20 in the neoplastic cells. The results showed the importance of the cytogenetic analysis in relation to leukemia, its direct benefits to the patients and the biological mechanisms involved in this disease. They also allowed the introduction in the Genetic Service of FAMERP techniques to obtain the bone marrow metaphases and the FISH technique.

Padronização e implementação da técnica de pesquisa de mutação JAK2V617F no Laboratório de Biologia Molecular do Hemocentro de Botucatu e correlação da presença do transcrito bcr-abl nos pacientes com doença mieloproliferativa crônica

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Clinical outcome in chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation: The experience of the Bone Marrow Transplantation Unit of FUNFARME/BRAZIL using FISH

Investigation of the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in chronic myeloid leukemia patients is essential to predict prognosis and survival. In 20 patients treated at the Bone Marrow Transplantation Unit of São José do Rio Preto (São Paulo, Brazil), we used fluorescence in situ hybridization (FISH) to investigate the frequency of cells with BCR/ABL rearrangement at diagnosis and at distinct intervals after allo-HSCT until complete cytogenetic remission (CCR). We investigated the disease-free survival, overall survival in 3 years and transplant-related mortality rates, too. Bone marrow samples were collected at 1, 2, 3, 4, 6, 12, and 24 months after transplantation and additional intervals as necessary. Success rate of the FISH analyses was 100%. CCR was achieved in 75% of the patients, within on average of 3.9 months; 45% patients showed CCR within 60 days after HSCT. After 3 years of the allo-HSCT, overall survival rate was 60%, disease-free survival was 50% and the transplant-related mortality rate was 40%. The study demonstrated that the BCR-ABL FISH assay is useful for follow-up of chronic myeloid leukemia patients after HSCT and that the clinical outcome parameters in our patient cohort were similar to those described for other bone marrow transplantation units. ©FUNPEC-RP.

Perfil global de expressão de micro-RNAS circulantes como marcadores de resposta terapêutica na leucemia mielóide crônica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

STEAP1 protein overexpression is an independent marker for biochemical recurrence in prostate carcinoma

Aims: To investigate the prognostic value of expression levels of the genes STEAP1 and STEAP2, and of STEAP1 protein, in prostate carcinomas (PCa). Methods and results: STEAP1 and STEAP2 transcript levels were evaluated by RT-qPCR in samples from 35 PCa, 24 adjacent non-neoplastic prostate (AdjP) tissues, five cases of benign prostatic hyperplasia (BPH), and two histologically normal prostates (N). STEAP1 expression was assessed by immunohistochemistry in samples from 198 PCa, 76 AdjP, 22 BPH, and two N. The findings were compared with clinical and pathological parameters and patient outcome. STEAP1 and STEAP2 transcript analysis showed no differences between the groups tested. Although not significant, higher STEAP1 mRNA levels were detected in tumours with high Gleason scores and in patients who presented with biochemical recurrence (BCR). STEAP1 overexpression was detected in PCa, and was significantly associated with high-grade Gleason scores, seminal vesicle invasion, BCR, and worse outcome (metastasis or PCa-specific death). STEAP1 overexpression was significantly associated with shorter BCR-free survival. Multivariate analysis revealed that STEAP1 is an independent marker for BCR. Conclusions: These findings provide evidence that STEAP1 is a biomarker of worse prognosis in PCa patients. © 2013 John Wiley & Sons Ltd.