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Browsing by Author "FONSECA, S."

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  • Clinicobiological, immunophenotypic, and molecular characteristics of monoclonal CD56‐/+dim chronic natural killer cell large granular lymphocytosis.
    Publication . LIMA, M.; ALMEIDA, J.; MONTERO, A.G.; TEIXEIRA M DOS, A.; QUEIROS, M.L.; SANTOS, A.H.; BALANZATEGUI, A.; ESTEVINHO, A.; ALGUERO MDEL, C.; BARCENA, P.; FONSECA, S.; AMORIM, M.L.; CABEDA, J.M.; PINHO, L.; GONZALEZ, M.; SAN MIGUEL, J.; JUSTICA, B.; ORFAO, A.
    Am J Pathol. 2004 Oct;165(4):1117-27. Clinicobiological, immunophenotypic, and molecular characteristics of monoclonal CD56-/+dim chronic natural killer cell large granular lymphocytosis. Lima M, Almeida J, Montero AG, Teixeira Mdos A, Queirós ML, Santos AH, Balanzategui A, Estevinho A, Algueró Mdel C, Barcena P, Fonseca S, Amorim ML, Cabeda JM, Pinho L, Gonzalez M, San Miguel J, Justiça B, Orfão A. Serviço de Hematologia, Unidade de Citometria, Hospital Geral de Santo António, Rua D Manuel II, s/n, 4099-001 Porto, Portugal. mmc.lima@clix.pt. Abstract Indolent natural killer (NK) cell lymphoproliferative disorders include a heterogeneous group of patients in whom persistent expansions of mature, typically CD56(+), NK cells in the absence of any clonal marker are present in the peripheral blood. In the present study we report on the clinical, hematological, immunophenotypic, serological, and molecular features of a series of 26 patients with chronic large granular NK cell lymphocytosis, whose NK cells were either CD56(-) or expressed very low levels of CD56 (CD56(-/+dim) NK cells), in the context of an aberrant activation-related mature phenotype and proved to be monoclonal using the human androgen receptor gene polymerase chain reaction-based assay. As normal CD56(+) NK cells, CD56(-/+dim) NK cells were granzyme B(+), CD3(-), TCRalphabeta/gammadelta(-), CD5(-), CD28(-), CD11a(+bright), CD45RA(+bright), CD122(+), and CD25(-) and they showed variable and heterogeneous expression of both CD8 and CD57. Nevertheless, they displayed several unusual immunophenotypic features. Accordingly, besides being CD56(-/+dim), they were CD11b(-/+dim) (heterogeneous), CD7(-/+dim) (heterogeneous), CD2(+) (homogeneous), CD11c(+bright) (homogeneous), and CD38(-/+dim) (heterogeneous). Moreover, CD56(-/+dim) NK cells heterogeneously expressed HLA-DR. In that concerning the expression of killer receptors, CD56(-/+dim) NK cells showed bright and homogeneous CD94 expression, and dim and heterogeneous reactivity for CD161, whereas CD158a and NKB1 expression was variable. From the functional point of view, CD56(-/+dim) showed a typical Th1 pattern of cytokine production (interferon-gamma(+), tumor necrosis factor-alpha(+)). From the clinical point of view, these patients usually had an indolent clinical course, progression into a massive lymphocytosis with lung infiltration leading to death being observed in only one case. Despite this, they frequently had associated cytopenias as well as neoplastic diseases and/or viral infections. In summary, we describe a unique and homogeneous group of monoclonal chronic large granular NK cell lymphocytosis with an aberrant activation-related CD56(-/+dim)/CD11b(-/+dim) phenotype and an indolent clinical course, whose main clinical features are related to concomitant diseases. PMID: 15466379 [PubMed - indexed for MEDLINE]PMCID: PMC1618630
    2004-10Journal article Open access Show more
  • Guess what: Chronic 13q14.3+/CD5‐ /CD23+ lymphocytic leukemia in blood and t(11;14)(q13;q32)+/CD5+/CD23‐ mantle cell lymphoma in lymph nodes!
    Publication . LIMA, M.; PINTO, L.; DOS ANJOS TEIXEIRA, M.; CANELHAS, A.; MOTA, A.; CABEDA, J.M.; SILVA, C.; QUEIROS, M.L.; FONSECA, S.; SANTOS, A.H.; BROCHADO, P.; JUSTICA, B.
    Cytometry B Clin Cytom. 2003 Jan;51(1):41-4. Guess what: Chronic 13q14.3+/CD5-/CD23+ lymphocytic leukemia in blood and t(11;14)(q13;q32)+/CD5+/CD23- mantle cell lymphoma in lymph nodes! Lima M, Pinto L, Dos Anjos Teixeira M, Canelhas A, Mota A, Cabeda JM, Silva C, Queirós ML, Fonseca S, Santos AH, Brochado P, Justiça B. Service of Clinical Hematology, Hospital Geral de Santo António, Porto, Portugal. mmc.lima@clix.pt Abstract We report a case of a patient with two B-cell lymphoproliferative disorders: CD5(-)/CD23(+) B-cell chronic lymphocytic leukemia and CD5(+)/CD23(-) mantle cell lymphoma. These disorders were diagnosed simultaneously based on flow cytometry, immunohistochemistry, fluorescence in situ hybridization, and polymerase chain reaction-based molecular studies. The B-cell lymphocytic leukemia clone predominated in the blood and bone marrow, whereas the mantle cell clone predominated in lymph nodes. Copyright 2002 Wiley-Liss, Inc. PMID: 12500296 [PubMed - indexed for MEDLINE]
    2003-01Journal article Open access Show more
  • Immunophenotypic aberrations, DNA content, and cell cycle analysis of plasma cells in patients with myeloma and monoclonal gammopathies
    Publication . LIMA, M.; TEIXEIRA MDOS, A.; FONSECA, S.; GONCALVES, C.; GUERRA, M.; QUEIROS, M.L.; SANTOS, A.H.; COUTINHO, A.; PINHO, L.; MARQUES, L.; CUNHA, M.; RIBEIRO, P.; XAVIER, L.; VIEIRA, H.; PINTO, P.; JUSTICA, B.
    Blood Cells Mol Dis. 2000 Dec;26(6):634-45. Immunophenotypic aberrations, DNA content, and cell cycle analysis of plasma cells in patients with myeloma and monoclonal gammopathies. Lima M, Teixeira Mdos A, Fonseca S, Gonçalves C, Guerra M, Queirós ML, Santos AH, Coutinho A, Pinho L, Marques L, Cunha M, Ribeiro P, Xavier L, Vieira H, Pinto P, Justiça B. Service of Clinical Hematology, Hospital Geral de Santo António, Rua D Manual II, s/n, 4050 Porto, Portugal. m.lima@ip.pt Abstract We describe the immunophenotypic and gross DNA defects in 55 patients with myeloma and 50 patients with monoclonal gammopathy and review the literature on this subject (MedLine, 1994-2000). Our data confirmed previous reports indicating that in myeloma nearly all marrow plasma cells are abnormal (98.7 +/- 8.1%). In monoclonal gammopathy the fraction of abnormal plasma cells was 35.0 +/- 32.8%. In both myeloma and monoclonal gammopathy, the most frequent aberrant phenotypic features consisted of absence of expression of CD19, strong expression of CD56, and decreased intensity of expression of CD38; aberrant expression of CD10, CD20, CD22, or CD28 was observed in less than one-third of myeloma cases. The vast majority of cases had two or more phenotypic aberrations. In the DNA studies, 7% of myeloma cases were biclonal and 93% of cases were monoclonal. In those studies with only one plasma cell mitotic cycle, 37% had normal DNA content and 63% were aneuploid (hyperploid, 61%; hypoploid, 2%). The mean percentages of plasma cells in S- and G2M phases were 4.9 +/- 8.5 and 4.4 +/- 6.9%, respectively. Thirty-eight percent of cases had more than 3% of plasma cells in S phase. In monoclonal gammopathy, the DNA index of abnormal plasma cells ranged from 0.89 to 1.30 and the percentage of diploid (31%) and aneuploid (69%) cases was not different from the results found in myeloma. The differences in percentage of abnormal plasma cells in S- (7.4 +/- 8.6%) and G2M-phases (2.4 +/- 1.7%) in patients with monoclonal gammopathy were not statistically significant. Copyright 2000 Academic Press. PMID: 11358356 [PubMed - indexed for MEDLINE]
    2000-12Journal article Open access Show more
  • Reactive phenotypes after acute and chronic NK‐cell activation
    Publication . LIMA, M; ALMEIDA, J.; TEIXEIRA, M.A.; SANTOS, A.H.; QUEIROS, M.L.; FONSECA, S.; MOURA, J.; GONCALVES, M.; ORFAO, A.; PINTO RIBEIRO, A.C.
    J Biol Regul Homeost Agents. 2004 Jul-Dec;18(3-4):331-4. Reactive phenotypes after acute and chronic NK-cell activation. Lima M, Almeida J, Teixeira MA, Santos AH, Queirós ML, Fonseca S, Moura J, Gonçalves M, Orfão A, Pinto Ribeiro AC. Service of Clinical Hematology, Laboratory of Cytometry, Hospital Geral de Santo António, Porto, Portugal. mmc.lima@clix.pt Abstract Several phenotypic changes have been shown to occur after NK-cell stimulation, involving molecules that have been proved to regulate NK-cell migration into tissues and NK-cell activation and proliferation as well as target cell recognition and killing. Here, we review the reactive phenotypes observed in vivo after acute and chronic NK-cell activation. PMID: 15786700 [PubMed - indexed for MEDLINE]
    2004-07Journal article Open access Show more
  • TCRalphabeta+/CD4+ large granular lymphocytosis: a new clonal T‐cell lymphoproliferative disorder.
    Publication . LIMA, M.; ALMEIDA, J.; DOS ANJOS TEIXEIRA, M.; ALGUERO, M.D.; MDEL, C.; SANTOS, A.H.; BALANZATEGUI, A.; QUEIROS, M.L.; BARCENA, P.; IZARRA, A.; FONSECA, S.; BUENO, C.; JUSTICA, B.; GONZALEZ, M.; SAN MIGUEL, J.F.; ORFAO, A.
    Am J Pathol. 2003 Aug;163(2):763-71. TCRalphabeta+/CD4+ large granular lymphocytosis: a new clonal T-cell lymphoproliferative disorder. Lima M, Almeida J, Dos Anjos Teixeira M, Alguero Md Mdel C, Santos AH, Balanzategui A, Queirós ML, Bárcena P, Izarra A, Fonseca S, Bueno C, Justiça B, Gonzalez M, San Miguel JF, Orfao A. Serviço de Hematologia Clinica, Unidade de Citometria, Hospital Geral de Santo Antonio, Porto, Portugal. Abstract Large granular lymphocyte (LGL) leukemia is a well-recognized disease of mature T-CD8(+) or less frequently natural killer cells; in contrast, monoclonal expansions of CD4(+) T-LGL have only been sporadically reported in the literature. In the present article we have explored throughout a period of 56 months the incidence of monoclonal expansions of CD4(+) T-LGL in a population of 2.2 million inhabitants and analyzed the immunophenotype and the pattern of cytokine production of clonal CD4(+) T cells of a series of 34 consecutive cases. Like CD8(+) T-LGL leukemias, CD4(+) T-LGL leukemia patients have an indolent disease; however, in contrast to CD8(+) T-LGL leukemias, they do not show cytopenias and autoimmune phenomena and they frequently have associated neoplasias, which is usually determining the clinical course of the disease. Monoclonal CD4(+) T-LGLshowed expression of TCRalphabeta, variable levels of CD8 (CD8(-/+dim)) and a homogeneous typical cytotoxic (granzyme B(+), CD56(+), CD57(+), CD11b(+/-)) and activated/memory T cell (CD2(+bright), CD7(-/+dim), CD11a(+bright), CD28(-), CD62L(-) HLA-DR(+)) immunophenotype. In addition, they exhibited a Th1 pattern of cytokine production [interferon-gamma(++), tumor necrosis factor-alpha(++), interleukin (IL-2)(-/+), IL-4(-), IL-10(-), IL-13(-)]. Phenotypic analysis of the TCR-Vbeta repertoire revealed large monoclonal TCR-Vbeta expansions; only a restricted number of TCR-Vbeta families were represented in the 34 cases analyzed. These findings suggest that monoclonal TCRalphabeta(+)/CD4(+)/NKa(+)/CD8(-/+dim) T-LGL represent a subgroup of monoclonal LGL lymphoproliferative disorders different from both CD8(+) T-LGL and natural killer cell-type LGL leukemias. Longer follow-up periods are necessary to determine the exact significance of this clonal disorder.
    2003-08Journal article Open access Show more