A Pérez-Losada

Catalonia Reference Laboratory, Barcino, Catalonia, Spain

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Publications (12)25.1 Total impact

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    ABSTRACT: We present the cytological features, conventional cytogenetics, and in situ hybridization (ISH) findings of three cases of B-cell prolymphocytic leukemia (B-PLL). The diagnosis was made according to the French-American-British (FAB) criteria. We considered a diagnosis of B-PLL when a predominance (> 50%) of lymphoid cells with coarse chromatin but prominent central nucleoli and more abundant cytoplasm than typical chronic lymphocytic leukemia (CLL) cells were present. B-PLL express strong SIg, B-cell antigens, and reactivity with the monoclonal antibody FMC7. Chromosome analysis was carried out on lymphoid cells from peripheral blood and, in one patient, from lymph node. The phytohemagglutinin (PHA) mitogen was used. ISH was performed with two types of probes: the biotin-labeled chromosome 12-specific alpha satellite DNA probe to detect trisomy 12, and biotin-labeled libraries of whole chromosomes 1, 7, and 14. Clonal chromosome abnormalities were found in all three patients; in one, a complex karyotype was observed. The most frequent recurrent abnormality was trisomy 12. Our results suggest that PLL usually presents with cytogenetic abnormalities. The finding of translocation (11;14) is noteworthy; chromosomes 1 and 3 are also involved.
    Cancer Genetics and Cytogenetics 05/1998; 103(1):43-5. · 1.93 Impact Factor
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    ABSTRACT: We describe the cytogenetic results of 93 patients with myelodysplastic syndromes (MDS). The main object of this report is to analyze the prognostic value of the karyotype in patients with MDS, in relation to the evolution to acute leukemia and the survival time. Cytogenetic studies were performed in 93 untreated cases of MDS between 1985 and 1994. Overall survival and the evolution to acute leukemia were analyzed. Among 93 patients who were examined at the time of diagnosis, 40 had an abnormal karyotype (43%). The highest frequency of chromosome abnormalities was observed in refractory anaemia with excess of blasts (RAEB) (65.7%) and RAEB in transformation (RAEB-t) (40%) and the lowest in refractory anaemia with ringed sideroblasts (RARS) (10%). The chromosomes most frequently involved were: 5, 7, 8, 11, 12 and 17. No relationship was found between FAB subtypes and the type of chromosomal abnormalities. In respect to the prognosis, an abnormal karyotype, and a complex karyotype were related with a higher frequency of evolution to acute leukemia. A model based on karyotype could divide patients in two groups: poor prognosis (patients with an abnormal karyotype, with involvement of chromosome 7, trisomy 8 or with a complex karyotype), and a good prognosis (patients with normal karyotype). The cytogenetic studies are very useful in the study of MDS for their clinical implications.
    Medicina Clínica 01/1998; 110(3):94-8. · 1.25 Impact Factor
  • A Pérez-Losada, S Woessner, F Solé, L Florensa
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    ABSTRACT: Banding techniques are essential in the chromosomal analysis for the cytogenetic diagnosis. Even that, conventional cytogenetic techniques destroy the cytoplasmic membrane and the lineage involvement of the karyotyped cells is unknown. In this work the usefulness of a method that keeps the cell intact and allows the sequential application of immunological, cytochemical, morphological and cytogenetic techniques in the same cell is shown. This technique is called MAC for morphology, antibodies and chromosomes. The combination of MAC and in situ hybridization techniques (MACISH method) allows the detection of a chromosome abnormality in all the cells even when no mitosis are present. The MAC method was applied in 51 patients and the MACISH method in 9 patients in order to identify the cells which karyotype is analyzed. We have studied 47 patients with normal karyotype (37 chronic lymphocytic leukaemia [CLL] and 10 essential trombocythaemias (ET) and 4 patients with different diseases and abnormal karyotype. Among 37 patients with CLL and normal karyotype, in 9 cases only normal T-cells were in mitoses and in 28 cases the normal karyotype belonged to neoplastic B cells. Trisomy 12 has been confined exclusively to the leukaemic B cells with the MACISH technique in 3 of these CLL cases. In 10 patients with ET and normal karyotype the MAC method showed that in any case the mitosis analyzed belonged to the megakaryocyte lineage. In 4 patients with different chromosomal abnormalities the haematological cell lines involved in the neoplasia were known with the MAC method. In this work is shown the usefulness of the combination of the MAC and MACISH techniques with conventional cytogenetics in order to complete the chromosomic study of the haematological neoplasms is confirmed. These methods are specially usefull when different cell lineages are involved in the neoplasia, reactive proliferations are suspected, or to discard false aneuploidies.
    Medicina Clínica 12/1997; 109(16):611-4. · 1.25 Impact Factor
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    ABSTRACT: The results of cytogenetic studies are reported in 76 patients with B-chronic lymphoproliferative disorders (B-CLPD): 60 patients with chronic lymphocytic leukemia (CLL), six with follicular lymphoma in leukemic phase (FLLP), five with splenic B-cell lymphoma with villous lymphocytes (SLVL), two with chronic prolymphocytic leukemia (CPL), two with hairy cell leukemia (HCL), and one with plasma cell leukemia (PCL). PHA (phytohemagglutinin), PWM (pokeweed mitogen), LPS (lipopolysaccharide from Escherichia Coli), TPA (phorbol 12-myristate acetate), IL6 (interleukin 6), and DxS (dextran sulfate) were used as mitogens. Mitoses were obtained in 75 cases. Clonal aberrations could be demonstrated in 34 cases (44%). In CLL, classical type, chromosomes 6, 11, and 13 were more frequently involved, whereas trisomy 12 was frequently found in CLL mixed-cell type, in FLLP, and CPL. In SLVL the deletion del(7)(q32) is noteworthy and miscellaneous chromosome abnormalities in the remaining patients were observed. Regarding the efficiency of mitogens, PHA turned to be the most effective in obtaining metaphases and in detecting clonal chromosomal aberrations.
    Cancer Genetics and Cytogenetics 03/1997; 93(2):160-6. · 1.93 Impact Factor
  • S Woessner, F Solé, A Pérez-Losada, L Florensa, R M Vilá
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    ABSTRACT: We have studied 61 cases of B-chronic lymphocytic leukemia (CLL), combining cytological features, conventional cytogenetics and in situ hybridization (ISH). The comparison of these results constitutes the main subject of this study. The patients were cytologically classified according to the FAB criteria as: chronic lymphocytic leukemia (CLL) typical type (48 cases) and CLL atypical types (13 cases). Chromosome analysis was carried out on lymphoid cells from peripheral blood. The following mitogens were used: phytohemagglutinin (PHA) 5%, pokeweed (PWM) and lipopolysaccharide from E. coli. The ISH was performed with a biotin-labeled, chromosome 12-specific alpha satellite DNA probe, pSP12-1. Trisomy 12 was not found in any of the 48 patients with the typical type of CLL and in contradistinction it was present in some patients with atypical types. This study emphasizes the great importance of a closer link between hematological morphology and the cytogenetic approach.
    Leukemia Research 06/1996; 20(5):369-74. · 2.76 Impact Factor
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    ABSTRACT: Mantle cell lymphomas (MCLs) are molecularly characterized by bcl-1 rearrangement and constant cyclin D1 (PRAD-1/CCND1) gene overexpression. Cyclin D1 is a G1 cyclin that participates in the control of the cell cycle progression by interacting with the retinoblastoma gene product (pRb). Inactivation of the Rb tumor suppressor gene has been implicated in the development of different types of human tumors including some high grade non-Hodgkin's lymphomas. To determine the role of the retinoblastoma gene in the pathogenesis of MCLs and its possible interaction with cyclin D1, pRb expression was examined in 23 MCLs including 17 typical and 6 blastic variants by immunohistochemistry and Western blot. Rb gene structure was studied in 13 cases by Southern blot. Cytogenetic analysis was performed in 5 cases. The results were compared with the cyclin D1 mRNA levels examined by Northern analysis, and the proliferative activity of the tumors was measured by Ki-67 growth fraction and flow cytometry. pRb was expressed in all MCLs. The expression varied from case to case (mean, 14.1% of positive cells; range, 1.3 to 42%) with a significant correlation with the proliferative activity of the tumors (mitotic index r = 0.85; Ki-67 r = 0.7; S phase = 0.73). Blastic variants showed higher numbers of pRb-positive cells (mean, 29%) than the typical cases (10%; P < 0.005) by immunohistochemistry and, concordantly, higher levels of expression by Western blot. In addition, the blastic cases also had an increased expression of the phosphorylated protein. No alterations in Rb gene structure were observed by Southern blot analysis. Cyclin D1 mRNA levels were independent of pRb expression and the proliferative activity of the tumors. These findings suggest that pRb in MCLs is normally regulated in relation to the proliferative activity of the tumors. Cyclin D1 overexpression may play a role in the maintenance of cell proliferation by overcoming the suppressive growth control of pRb.
    American Journal Of Pathology 06/1996; 148(5):1591-600. · 4.60 Impact Factor
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    ABSTRACT: Cytogenetic analysis was successfully performed in 45 consecutive multiple myeloma (MM) patients. Cytogenetic abnormalities were observed in 13 of 45 patients (29%). Eleven patients showed numerical changes and 9 showed structural abnormalities in chromosomes 5, 9, 11, 14, 15, and 19 were most frequently gained. Structural abnormalities preferentially involved chromosomes 6, 13, and 14.
    Cancer Genetics and Cytogenetics 03/1996; 86(2):162-4. · 1.93 Impact Factor
  • Cancer Genetics and Cytogenetics 07/1995; 81(2):185. · 1.93 Impact Factor
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    ABSTRACT: Isochromosome(12p), a cytogenetic abnormality characteristic of germ-cell tumors, is exceedingly rare in hematologic disorders. The cytogenetic analysis of a patient diagnosed as refractory anemia with excess of blasts with an associated i(12p), who previously had a teratocarcinoma of the mediastinum, is presented. The cytogenetic analysis was performed at diagnosis of the hematologic malignancy, with all 30 metaphases in the bone marrow culture showing a 47,X, -Y, +8, +i(12)(p10) karyotype. The cytogenetic findings in this patient are compared with those published concerning the association of mediastinal germ-cell tumors and malignant hematologic disorders.
    Cancer Genetics and Cytogenetics 11/1994; 77(2):111-3. · 1.93 Impact Factor
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    ABSTRACT: We report a case of multiple myeloma with a t(8;22)(q24;q11) found during the progression of the disease. The relation between the association of a Burkitt's type translocation with cytological characteristic features is presented. To our knowledge, there is no report of a multiple myeloma with t(8;22)(q24;11).
    Leukemia Research 10/1994; 18(9):671-3. · 2.76 Impact Factor
  • Cancer Genetics and Cytogenetics 08/1994; 75(1):72-3. · 1.93 Impact Factor
  • A Pérez-Losada, S Woessner, F Solé, L Florensa, A Grañena
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    ABSTRACT: We report a case with refractory anaemia terminating in an acute leukaemia, which showed from the very beginning an intense eosinophilia that lasted for the whole disease, and in which the eosinophilic metaphases, as documented by the 'Morphology, Antibody, Chromosome' technique, were normal. An unusual karyotypic anomaly in the setting of a myelodysplastic syndrome could only be detected in the neutrophilic series. A general approach to detect structural aberrations of specific human chromosomes in metaphase cells by chromosomal in situ suppression hybridization of DNA libraries from sorted human chromosomes has been applied for chromosomes 11, 3 and 2, in order to identify an extra copy of chromosome 2.
    Acta Haematologica 02/1994; 91(2):80-3. · 0.89 Impact Factor