The significance of major and stable molecular responses in chronic myeloid leukemia in the tyrosine kinase inhibitor era

Tyrosine kinase inhibitors have changed the management and outcomes of chronic myeloid leukemia patients. Quantitative polymerase chain reaction is used to monitor molecular responses to tyrosine kinase inhibitors. Molecular monitoring represents the most sensitive tool to judge chronic myeloid leukemia disease course and allows early detection of relapse. Evidence of achieving molecular response is important for several reasons: 1. early molecular response is associated with major molecular response rates at 18-24 months; 2. patients achieving major molecular response are less likely to lose their complete cytogenetic response; 3. a durable, stable major molecular response is associated with increased progression-free survival. However, standardization of molecular techniques is still challenging.

Burkitt-like lymphoma in an infant: a case report

Childhood non-Hodgkin's lymphomas, including Burkitt and Burkitt-like, are rarely diagnosed in infants. A case of B-cell lymphoma in a 13-month-old girl with extensive abdominal disease, ascites, pleural effusion, and tumor lysis syndrome is reported. Phenotypic analysis showed a germinal center B-cell phenotype, and a B-cell clonality was confirmed by polymerase chain reaction. There was no evidence of Epstein-Barr and HIV infection. The case herein reported emphasizes the need for considering the diagnosis of lymphoma even in very young children

Biologia e perfil imunocelular das leucemias: rearranjo gênico em desordens linfoproliferativas

Estudos multidisciplinares de pacientes com leucemia podem determinar a origem celular, clonalidade das células envolvidas e alterções gênicas de valor diagnóstico e prognóstico, contribuindo para a melhoria destes, e para a detecção de genes, envolvidos no processo de transformação maligna. Estes estudos, aqui apresentados, tem sido úteis para o estabelecimento de uma classificação das leucemias linfociticas e linfobláticas. Um estudo da distribuição da doença foi feito em um grupo padrão de LeucemiasLinfóides Agudas (LLA) da infância.A análise imunológica de fluxo foi realizada em 152 pacientes. A análise molecular dos genes das Imunoglobinas (Ig) e do Receptor de Células T (RCT) foi usado para determinar a origem celular das Leucemias Linfóides Agudas T (LLA T) mais indiferenciadas, leucemias bifenotípicas e Leucemias Agudas de origem Indeterminada (LAI), definidas pela imunofenotipagem. Estes estudos foram úteis para aferir a oriegem celular dos casos indeterminados e redefinir o grupo de leucemias bifenotípicas em leucemias de origem mielóide ou multipotente. A percentagem de rearranjos inapropriados dos genes da Ig e do RCT nos casos de LLA de origem T e B respectivamente sugerem o uso de rotina da abordagem molecular para a classificação e entendimento biológico das LLAs.A utilização da reação em cadeia pela polimerase (PCR) para determinação da clonalidae nas leucemias T e B de acordo com a imunofenotipagem mostrou resultados consistentes. A técnica de PCR deve ser utilizada preferencialmente à imunofenotipagem nos casos de desordens linfoproliferativas T. Uma vez implantado, nosso protocolo possibilitou a avaliação de doença residual mínima e recaída.Finalmente, o estudo dos aspectos biológicos das leucemias em geral e da regulação dos genes da Ig e do RCT em particular, à partir do estudo do desenvolvimento das regiões 14q32 e 14q11 onde se situam os genes das Ig e o RCT, respectivamente, em diferentes tipos de LLA foi realizado.O estabelecimento de uma nova linhagem celular (cemo-1) possibilitou a clonagem de um novo oncogenese, o BCL-9.

Multidisciplinary studies of leukaemic patients may precisely identify cellular origin, clonality and genomic rearrangements, providing valuable data for diagnosis, prognosis and for the identification of genes involved in malignant transformation. These studies, herein carried out, have been most helpful in establishing a classification of lymphoblastic and lymphocytic leukaemias. Different aspects of the disease were studied in a standard group of childhooh Acute Lymphoblastic Leukaemias. Immunologic analyses, with flow cytometry, were carried out in 152 patients while molecular analyses of Immunoglobulin (Ig) and T-cell receptor (TCR) genes were used for determining the cellular origin of the acute, most-undifferentiated lymphoblastic leukaemias, biphenotypic leukaemias, and leukaemias of unknown origin previously characterized by immunophenotyping. These analyses were useful for identifying unknown cellular origin as well as for reconsidering the group of bifenotypic leukaemias in respect to myeloid or multipotent origins. The percentage of inapropriate Ig and TCR gene rearrangements in T and B acute lymphoblastic leukaemias respectively indicated that molecular analyses must be routinely used for understanding the biology of the disease. The use of PCR in conjunction with immunophenotyping for diagnosing clonality in T and B leukaemias showed consistent results in B cell leukaemias. Conversely, PCR was preferable to immunophenotyping for diagnosis of T cell leukaemias. Our protocol, once established, was also useful for monitoring minimum residual disease and relapse. Finally, general aspects of leukaemia biology, regulation of Ig and TCR genes, and involvements of l4q32 and l4qll regions, where these genes are respectively located, were studied in different types of acute leukaemias. The establishment of a new cell line (CEMO-l) lead to the identification and cloning of the new oncogene BCL-9.