Browsing by Author "BALANZATEGUI, A."
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- Association of CD4+/CD56+/CD57+/CD8+(dim) large granular lymphocytic leukemia, splenic B‐cell lymphoma with circulating villous lymphocytes, and idiopathic erythrocytosisPublication . LIMA, M.; GONCALVES, C.; MARQUES, L.; MARTIN, M.C.; TEIXEIRA, M.A.; QUEIROS, M.L.; SANTOS, A.H.; BALANZATEGUI, A.; GARCIA‐SANZ, R.; PINTO‐RIBEIRO, A.C.; JUSTICA, B.; ORFAO, A.Ann Hematol. 2001 Nov;80(11):685-90. Association of CD4+/CD56+/CD57+/CD8+(dim) large granular lymphocytic leukemia, splenic B-cell lymphoma with circulating villous lymphocytes, and idiopathic erythrocytosis. Lima M, Gonçalves C, Marques L, Martin MC, Teixeira MA, Queirós ML, Santos AH, Balanzategui A, Garcia-Sanz R, Pinto-Ribeiro AC, Justiça B, Orfão A. Service of Clinical Hematology, Hospital Geral Santo António, Porto, Portugal. mmc.lima@clix.pt Abstract In this paper we report a rare association of a splenic marginal zone B-cell lymphoma with villous lymphocytes and a T-cell large granular lymphocytic leukemia coexpressing CD4 and CD8 as well as CD56 and CD57 natural killer-associated markers in an asymptomatic patient investigated because of an occasional finding of erythrocytosis and leukocytosis in routine blood analysis. We also discuss the possible reasons for this particular association. PMID: 11757730 [PubMed - indexed for MEDLINE]
- 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
- Immunophenotypic analysis of the TCR‐Vbeta repertoire in 98 persistent expansions of CD3(+)/TCR‐alphabeta(+) large granular lymphocytes: utility in assessing clonality and insights into the pathogenesis of the diseasePublication . LIMA, M.; ALMEIDA, J.; SANTOS, A.H.; DOS ANJOS TEIXEIRA, M.; ALGUERO, M.C.; QUEIROS, M.L.; BALANZATEGUI, A.; JUSTICA, B.; GONZALEZ, M.; SAN MIGUEL, J.F.; ORFAO, A.Am J Pathol. 2001 Nov;159(5):1861-8. Immunophenotypic analysis of the TCR-Vbeta repertoire in 98 persistent expansions of CD3(+)/TCR-alphabeta(+) large granular lymphocytes: utility in assessing clonality and insights into the pathogenesis of the disease. Lima M, Almeida J, Santos AH, dos Anjos Teixeira M, Alguero MC, Queirós ML, Balanzategui A, Justiça B, Gonzalez M, San Miguel JF, Orfão A. Serviço de Hematologia Clínica, Unidade de Citometria, Hospital Geral de Santo António, Porto, Portugal. mmc.lima@clix.pt Abstract At present, a major challenge in the initial diagnosis of leukemia of large granular lymphocytes (LGLs) is to establish the clonal nature of the expanded population. In the present study we have analyzed by flow cytometry immunophenotyping the TCR-Vbeta repertoire of 98 consecutive cases of persistent expansions of CD4(+) or CD8(+bright) CD3(+)/TCR-alphabeta(+) LGLs and compared the results with those obtained in molecular studies of TCR-beta gene rearrangements. Fifty-eight cases were considered to be monoclonal in molecular studies whereas in the remaining 40 cases there was no evidence for monoclonality (11 cases were considered oligoclonal and 29 polyclonal). The TCR-Vbeta repertoire was biased to the preferential use of one or more TCR-Vbeta families in 96% of cases, a total of 124 TCR-Vbeta expansions being diagnosed: one TCR-Vbeta expansion in 71 cases and two or more TCR-Vbeta expansions in 23 cases. The highest TCR-Vbeta expansion observed in each case was higher among monoclonal (74 +/- 19%) as compared to nonmonoclonal cases (24 +/- 14%) (P = 0.001), as did the fraction of LGLs that exhibited a TCR-Vbeta-restricted pattern (86 +/- 16% and 42 +/- 23%, respectively; P = 0.0001); by contrast, the proportion of cases displaying more than one TCR-Vbeta expansion was higher in the latter group: 7% versus 48%, respectively (P = 0.001). Results obtained in oligoclonal cases were intermediate between those obtained in polyclonal and monoclonal cases and similar results were observed for CD4(+) as for CD8(+bright) T-cell expansions. TCR-Vbeta families expressed in CD8(+bright) T-cell-LGL proliferations showed a pattern of distribution that mimics the frequency at which the individual TCR-Vbeta families are represented in normal peripheral blood T cells. Assuming that a given proliferation of LGLs is monoclonal whenever there is an expansion of a given TCR-Vbeta family of at least 40% of the total CD4(+) or CD8(+bright) T-cell compartment, we were able to predict clonality with a sensitivity of 93% and a specificity of 80%. By increasing the cut-off value to 60%, sensitivity and specificity were of 81% and 100%. In summary, our results suggest that flow cytometry immunophenotypic analysis of the TCR-Vbeta repertoire is a powerful screening tool for the assessment of T-cell clonality in persistent expansions of TCR-alphabeta(+) LGLs. PMID: 11696446 [PubMed - indexed for MEDLINE]PMCID: PMC1867049
- Intraclonal diversity in a Sezary syndrome with a differential response to 2‐deoxycoformycin of the two lymphoma cell populationsPublication . GRANJO, E.; LIMA, M.; LOPES, J.M.; CUNHA, N.; TEIXEIRA, M. A.; SANTOS, F.; CANDEIAS, J.; RESENDE, C.; SANTOS, A.H.; BALANZATEGUI, A.; ORFAO, A.; MATUTES, E.Br J Haematol. 2002 Dec;119(3):629-33. Intraclonal diversity in a Sezary syndrome with a differential response to 2-deoxycoformycin of the two lymphoma cell populations. Granjo E, Lima M, Lopes JM, Cunha N, Teixeira Mdos A, Santos F, Candeias J, Resende C, Santos AH, Balanzategui A, Orfão A, Matutes E. Department of Clinical Haematology, Hospital Geral de São João, Porto, Portugal. npp46740@mail.telpac.pt Abstract We report a case of Sezary syndrome with two abnormal CD4+ T-cell populations detected in the peripheral blood by flow cytometry immunophenotyping and DNA cell content, suggesting a biclonal T-cell lymphoproliferative disorder. Despite these findings, molecular analysis of the T-cell receptor genes was consistent with a monoclonal T-cell proliferation, supporting the existence of intraclonal diversity rather than a true biclonal disease. The patient achieved a transient response with 2-deoxycoformycin, with a selective decrease of the larger/hyperploid T-cell population; later on, an increased representation of this T-cell population was observed concomitantly with clinical relapse. PMID: 12437636 [PubMed - indexed for MEDLINE]
- 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.