Myeloproliferative syndrome of monosomy 7: a brief report

We report the case of a five-month-old black male infant who had recurrent episodes of respiratory infections and also presented anemia and enlargements of the spleen, liver and lymphnodes. Hematological analysis revealed morphological abnormalities with megaloblastic dyserythropoiesis, while fetal hemoglobin assaying showed normal levels. Conventional and molecular cytogenetic analysis revealed monosomy of chromosome 7. Despite all therapeutic efforts during allogenic bone marrow transplantation, the child died due to generalized infection. The clinical and genetic distinctions between monosomy 7 syndrome and myelodysplastic disorders in childhood are discussed.

The impact of addictional chromosomal abnormalities in response to imatinib mesylate therapy for chronic myeloid leukemia

Imatinib induces a complete cytogenetic response in more than 80% of newly diagnosed patients with chronicmyeloid leukemia (CML) in the chronic phase (CP) and in 41% of patients in the first chronic phase after failureof interferon- treatment. However, some patients do not respond completely. Therefore, according to moststudies, drug resistance in CML patients treated with imatinib is correlated with cytogenetic abnormalities acquiredduring treatment. In this study we analyzed 48 CML patients treated with imatinib mesylate after interferon- resistance in order to elucidate the impact of additional chromosomal abnormalities prior to imatinib in response to therapy. Cytogenetic abnormalities in addition to the Philadelphia chromosome (Ph) were detected in 33.3% of patients. Patients with Ph as the sole cytogenetic abnormality prior to imatinib therapy presented a major cytogeneticresponse and significantly longer median overall survival (p=0.006) than patients with additional chromosomalabnormalities. Therefore, in this group of patients, another choice of treatment should be considered, such as stemcell transplantation or combination regimens as appropriate. The present study indicates the importance of detecting a double Ph chromosome prior to imatinib therapy. Patients showing this abnormality did not respond to imatinib, thus indicating the abnormality's association with resistance. Our study suggests that classical cytogenetic analysisis still an important tool prior to and during follow-up of CML patients treated with imatinib.

Imatinibe induz à resposta citogenética completa em cerca de 80 por cento dos pacientes diagnosticados com leucemia mielóide crônica (LMC) em fase crônica (FC), e em 41 por cento dos pacientes em primeira FC após falha do tratamento com interferon-alfa. Alguns pacientes, entretanto, não respondem completamente. Em muitos estudos, a resistência à droga em pacientes tratados com imatinibe é correlacionada a alterações cromossômicas adquiridas durante o tratamento. No presente estudo, foram analisados 48 pacientes tratados com imatinibe após resistência ao interferon-alfa, com o objetivo de verificar o impacto das alterações cromossômicas adicionais ao Philadelphia (Ph), prévias à terapia com imatinibe. Alterações adicionais foram detectadas em 33,3 por cento dos pacientes. Pacientes com somente o cromossomo Ph apresentaram melhor taxa de resposta citogenética e sobrevida global significativa maior quando comparados com os pacientes que apresentavam alterações cromossômicas adicionais antes do início da terapia com imatinibe. Assim, nesse grupo de pacientes, a escolha de outra conduta terapêutica, como o transplante de células tronco-hematopoéticas ou regime de combinação de drogas, pode ser indicada. O presente estudo indica a importância do duplo Ph antesdo início da terapia com imatinibe. Todos os pacientes com esta alteração não responderam ao tratamento, sendo a mesma associada à resistência à droga. Este estudo sugere que a citogenética clássica permanece como uma ferramenta importante no monitoramento de pacientes portadores de LMC tratados com imatinibe.

Karyotype abnormalities and their clinical significance in a group of chronic myeloid leukemia patients treated with hematopoietic stem cell transplantation

CONTEXT AND OBJECTIVE: Following hematopoietic stem cell transplantation (HSCT), karyotyping is a valuable tool for monitoring engraftment and disease status. Few studies have examined the prognostic significance of karyotypes in patients who underwent HSCT for chronic myeloid leukemia (CML). The objective of this study was to evaluate the significance of pretransplantation cytogenetic status in relation to outcomes following HSCT in CML patients. DESIGN AND SETTING: Case series study at Instituto Nacional do Câncer (INCA), Rio de Janeiro, Brazil. METHODS: Cytogenetic analysis was performed by G banding on 39 patients treated with HSCT. RESULTS: Thirty-one patients were in the chronic phase and eight were in the accelerated phase. Prior to HSCT, additional chromosomal abnormalities on the Philadelphia (Ph) chromosome were found in 11 patients. The most frequent additional abnormality was a double Ph, which was observed in four cases. Following HSCT, full chimeras were observed in 31 patients (79.5 percent). Among these, 23 (82.3 percent) had presented Ph as the sole abnormality. Mixed chimeras were observed in seven patients, of which three had additional abnormalities. Only one case did not present any cytogenetic response. Five patients presented cytogenetic relapse associated with clinical relapse following HSCT. Twenty-seven patients are still alive and present complete hematological and cytogenetic remission. CONCLUSION: In our study, the presence of additional abnormalities was not associated with worse outcome and relapse risk. Also, no differences in survival rates were observed. Our study supports the view that classical cytogenetic analysis remains an important tool regarding HSCT outcome.

RESUMO CONTEXTO E OBJETIVO: Após o transplante de células tronco-hematopoéticas (TCTH), o cariótipo é uma ferramenta valiosa para monitorar o status do enxerto e da doença. Poucos estudos investigaram o significado prognóstico do cariótipo nos pacientes que se submeteram ao TCTH para leucemia mielóide crônica (LMC). O objetivo desse estudo foi verificar o significado dos achados citogenéticos pré-TCTH em pacientes portadores de LMC. TIPO DE ESTUDO E LOCAL: Série de casos. Instituto Nacional do Câncer (INCA), Rio de Janeiro, Brasil. METODOLOGIA: Foram realizados estudos citogenéticos por bandeamento G em 39 pacientes submetidos ao TCTH. RESULTADOS: Trinta e um pacientes estavam em fase crônica e oito em fase acelerada. Pré-TCTH, alterações cromossômicas adicionais ao cromossomo Philadelphia (Ph) foram observadas em 11 pacientes. A mais freqüente foi o duplo Ph observado em quatro casos. Após o TCTH, quimerismo total foi observado em 31 pacientes (79,5 por cento). Desses, 23 (82,3 por cento) apresentavam somente o cromossomo Ph. Quimerismo misto foi observado em sete pacientes, sendo três com alterações adicionais ao Ph. Um caso não apresentou resposta ao TCTH. Recaída citogenética associada com recaída clínica foi observada em cinco pacientes. Após o TCTH, 27 pacientes permanecem vivos e com remissão clínica e citogenética. CONCLUSÃO: Em nosso estudo a presença de alterações cromossômicas adicionais ao Ph, prévias ao TCTH, não foi associada com pior evolução, com risco de recaída, bem como não foi observada diferença entre as taxas de sobrevida. Nosso estudo sugere que a citogenética clássica permanece uma grande ferramenta no monitoramento do TCTH.

Chromosome 17 abnormalities and mutation of the TP53 gene: correlation between cytogenetics, flow cytometry and molecular analysis in three cases of chronic myeloid leukemia

Alterations involving the short arm of chromosome 17 (17p) during the progression of chronic myeloid leukemia (CML) have been described. This chromosomal region contains the tumor suppressor gene TP53 that may be an important factor in the evolution of this disease. In this study, we used flow cytometry and western blotting to assess p53 protein expression and single stranded conformational polymorphism to examine TP53 gene alterations in three patients with CML who showed alterations in 17p. Only the case with del(17)(p11) had p53 expression positive by flow cytometry and an abnormal migration pattern by SSCP analysis. The importance of the correlation between the results obtained with these techniques, as well as the clinical course of the patients, are discussed.