RESUMO
In myelodysplastic syndromes (MDS), the karyotype is one of the most significant prognostic markers with profound impact on differential diagnosis and therapeutic decisions. In a retrospective study, we examined karyotypes of bone marrow specimens of an oligocentric cohort comprising 529 patients with MDS to address the question how many metaphases need to be analyzed to detect even small cell clones with an appropriate expenditure. We found a statistically significant difference of the frequency of normal karyotypes in the patient group with 19 or less analyzed metaphases compared to the group with 20 or more metaphases analyzed (56% versus 47%, p=0.041). Furthermore, we demonstrate that the analysis of 25 or more metaphases can further improve the sensitivity of karyotype analysis and leads to the identification of additional clinically relevant abnormal clones or subclones in a substantial proportion of patients. In summary, our data suggest the examination of at least 20 metaphases in MDS.
Assuntos
Aberrações Cromossômicas , Síndromes Mielodisplásicas/genética , Humanos , Cariotipagem , Estudos RetrospectivosRESUMO
In myelodysplastic syndromes (MDS) chromosomal anomalies can be identified in 50-80% of patients. They have a diagnostic and prognostic impact and are increasingly considered for therapeutic decisions. Cytomorphology and cytogenetic analyses of bone marrow (bm) cells define the goldstandard to diagnose MDS patients and to document treatment response. We present a novel method using peripheral blood (pb) for frequent cytogenetic monitoring: after immunomagnetic cell separation circulating CD34+ cells were analysed by fluorescence in situ hybridization (FISH). We compared FISH analyses of enriched and non-enriched pb and bm cells with conventional chromosome banding analyses of bm metaphases: analysing circulating CD34+ cells by FISH is a sensitive, reliable method to measure the abnormal cell clones in pb. This method is practicable, non-invasive, representative for the clonal situation in the bm, and has a predictive value. Its feasibility was proven in a cohort of 27 MDS patients.
Assuntos
Antígenos CD34/análise , Células da Medula Óssea/patologia , Aberrações Cromossômicas , Hibridização in Situ Fluorescente/métodos , Síndromes Mielodisplásicas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Azacitidina/uso terapêutico , Cromossomos Humanos Par 7 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monossomia , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/tratamento farmacológicoRESUMO
Chronic myeloid leukemia (CML) is characterized by the presence of a t(9;22)(q34;q11.2), which leads to the well-known BCR-ABL1 fusion protein. We describe a patient who was diagnosed clinically with a typical CML but on cytogenetic analysis was found to have a t(9;22)(p24;q11.2). Chromosomal fluorescence in situ hybridization showed that the BCR gene locus spanned the breakpoint at band 22q11.2 but that the ABL1 gene was not rearranged. By means of a candidate gene approach, the JAK2 gene, at 9p24, was identified as the fusion partner of BCR in this case. The BCR-JAK2 fusion protein contains the coiled-coil dimerization domain of BCR and the protein tyrosine kinase domain (JH1) of JAK2. The patient's disease did not respond to Imatinib, and this unresponsiveness was most likely a result of the BCR-JAK2 fusion protein.
Assuntos
Cromossomos Humanos Par 22/genética , Cromossomos Humanos Par 9/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Proteínas de Fusão Oncogênica/genética , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas c-bcr/genética , Proteínas Proto-Oncogênicas/genética , Translocação Genética/genética , Antineoplásicos/uso terapêutico , Benzamidas , Feminino , Humanos , Mesilato de Imatinib , Hibridização in Situ Fluorescente , Janus Quinase 2 , Cariotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Pessoa de Meia-Idade , Piperazinas/uso terapêutico , Pirimidinas/uso terapêuticoRESUMO
Mantle cell lymphoma (MCL) is immunophenotypically characterized by cell surface co-expression of CD19, CD20, CD5, IgM and FMC7. However, the concomitant presence of other antigens distinctive of a particular leukocyte subset, e.g. T-lymphocytes, is an exceptional finding in MCL. Here, the first case of a blastic MCL in leukaemic phase with aberrant expression of the T-cell associated antigen CD8 occurring in a patient with concomitant Mycosis fungoides is described. Comprehensive immunophenotypic analysis showed that the MCL cells expressed the typical B-lymphocytic markers, were CD5 and CD8 positive, but did not express other T-cell proteins, such as CD2, CD3, CD4, CD7, TCRalphabeta and TCRgammadelta. The MCL cells expressed both CD8alpha and CD8beta chains indicating cell surface presence of CD8alphabeta heterodimers. Intriguingly, expression of the cytotoxic enzymes perforin and granzyme A was detected by RT-PCR. Cytogenetic and molecular genetic analysis of the lymphoma cells confirmed cyclin D1 overexpression secondary to the t(11;14)(q13;32) chromosomal translocation. Furthermore, trisomy 11, trisomy 14 and extra copies of t(11;14) translocated chromosomes were detected in sub clones of the analyzed MCL cells. Clinically, an aggressive course of disease including cerebral lymphoma involvement was noted in the reported patient. Hence, systematic studies addressing the incidence, biology and clinical behavior of this form of MCL seem to be justified in future.