HEMOPATOLOGY

Author: MUÑOZ MARÍN M. LUZ.
Year: 2004.
University: AUTÓNOMA DE BARCELONA.
Place of defense: HOSPITAL SANT PAU.
Place of preparation: ESCUELA DE POSTGRADO.

Summary: The acute leukemia is a clonal alteration of hematopoietic progenitors with a great heterogeneity from the point of view as biological clinic. Currently the management of patients with acute leukemia were stratified according to the classification and the presence of certain prognostic factors. There are various techniques useful in the diagnosis, classification and monitoring of patients with acute leukemia are as cytology, cytogenetics, flow cytometry and molecular biology and it is necessary to integrate all of them to get a correct characterization of acute leukemia. Thus defined entities clínico-biológicas with certain prognostic value and tax to a more individualized treatment. In this regard, analysis inmunofenotípico in acute leukemia is essential for a correct classification, provides prognostic information and more recently used in the study of minimal residual disease in remission. The overall objective of this thesis is to explore the value of characterization inmunofenotípica of acute leukemias, identify new markers and build partnerships with clinical and biological parameters, the latter places particular emphasis on correlation with molecular subgroups. It conducted an analysis of the expression of antigens CD66 and CD123 and discusses the characteristics clínico-biológicas and phenotypic characteristic pattern in the following alterations genético - moleculares with prognostic value in acute leukemia: bcr / abl in LLA- B; aml-1/eto, cbfb/myh-11, reordering of MLL and duplication of FLT3 in MAL. The antigen CD66 was expressed in 67% in the LLA-B, while the antigen CD123 was expressed in all patients with LLA-By in 93% of the MAL. In almost no change was detected reactivity of CD66 or CD123 in normal hematopoietic precursors. This suggests that these markers are useful in the study of minimal residual disease in patients with acute leukemia with a high applicability. The study of the detection of MRA in patients with LLA-Ph + by flow cytometry and RT-PCR showed a good correlation between the two techniques. However several samples were detected with discordant results. The sensitivity of the combination of both methods was superior to each of the techniques separately by what we believe that the combination of flow cytometry and RT-PCR is choice in the study of MRA in patients with LLA-B Ph + . In the series of patients with MAL, the frequency of aml-1/eto was 7%. These patients were significantly younger, were less infiltration of bone marrow blasts at diagnosis showed a greater percentage of complete remission induction therapy and showed greater overall survival than the rest of the series. The phenotypic pattern more typical was the presence of several subpopulations with immature myeloid antigen monocíticos variable expression. The frequency of cbfb/myh-11 was 8%. We found no differences in age, number of blasts or response to treatment induction. The patients in this group showed greater overall survival and less likely to relapse than the rest of the series but no significant differences. The phenotypic pattern more typical was the presence of several subpopulations with blastic phenotype mielomonocítico with high expression of antigens monocíticos. The frequency of gene rearrangement of the MLL was 12% and the partial duplication tandem was 8%. These patients had significantly greater percentage of monocytic leukemia, there were no differences in treatment response induction, but showed lower overall survival and greater likelihood of relapse. The pattern phenotypic characteristic of this lesion mo 8 lecular 5df is the presence of a single blast mielomonocítica mature people, in all cases was detected coexpresión antigen monocíticos. Finally, the last group was analyzed molecular duplication of the gene FLT3, which was the most common: 27%. These patients showed increased leukocytosis diagnosis, the greater percentage of monocytic leukemia and normal karyotype and lower overall survival and relapse more likely than the rest of the series. The most common phenotypic pattern was the presence of several subpopulations blastic mielomonotícias with high expression of antigens monocíticos and decrease antigen immaturity. These patients had a high genetic instability with frequent changes in the phenotypic and genotypic relapse.

Author: MARCÉ TORRA SILVIA.
Year: 2005.
University: BARCELONA.
Place of defense: FACULTAT MEDICINA.
Place of preparation: FACULTAT DE MEDICINA.

Summary: The LCM is a lymphoproliferative syndrome aggressive and highly resistant to current therapies. By studying the cytotoxic effect of fludarabine, mitoxantrone and cyclophosphamide elementary LCM cells and cells of cell lines probadoras of the t (11; 14) (q13, q32) is shown that the mitoxantrone, an inhibitor of topoisomerasa II exerts the greatest cytotoxic effect. In addition, the blast variant is more sensitive to mitoxantrone that variant typical possibly due to high levels of expression of topoisomerasa-II. In cases blásticos. The cytotoxicity induced by genotoxic these drugs is mediated by the activation of the path apotótica mitochondrial due to a year in the DNA, it is necessary that the sensors damage to DNA, p53 and / or ATM, are functional. The effect on dela fludarabine cells LLc-B is determined in the first instance by the transport route hENT2, ascribing importance for the first time in the therapeutic effect of a nucleoside analogue. The expression of this transporter correlated significantly with the cytotoxic effect induced by fludarabine cells LLC-B. However, LCM cells, which do not respond to fludarabine in vitro, express higher levels of mRNA and protein hENT1 that hENT2. This differential expression may explain the different response to fludarabine between cells LCM and LLC-B. The gemitabina, drug transported predominantly by hENT1, induces a cytotoxic effect on LCM cells at doses below those needed to fludarabine to exert the same effect, which suggests that an analysis of the expression of nucleoside transporters in cells LLC - By LCM is useful in the choice of therapy to continue and possibly to predict response to treatment. Cases of LCM presenting deletion of the gene APLs and loss of expression of the protein are associated with increased aggressiveness of the disease and a worse prognosis. This phenomenon is due, most likely, to the close relationship between the gene and APLs locus INK4a-ARF in these tumors, suggesting that the immunohistochemical detection of APLs can be a good marker for the loss of the entire locus. Furthermore, analysis of the expression of APLs can be a good tool to identify those patients who would benefit from therapy targeted by inhibiting the path of de novo synthesis of AMP. Our results support the idea of using the combination of L-alanosina and EFA as a treatment for such cases delección of APLs.

Author: CARVAJAL VERGARA XONIA.
Year: 2005.
University: SALAMANCA.
Place of defense: CENTRO DE INVESTIGACION DEL CANCER.
Place of preparation: CENTRO DE INVESTIGACION DEL CANCER.