Browsing by Author "ORFAO, A."
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- An unusual acute myeloid leukemia associated with hyper IgE: another case of AML‐M5c?Publication . LIMA, M.; ORFAO, A.; COUTINHO, J.; FERREIRA, G.; FREITAS, I.; SILVESTRE, F; JUSTICA, B.Haematologica. 2001 Feb;86(2):216-7. An unusual acute myeloid leukemia associated with hyper IgE: another case of AML-M5c? Lima M, Orfão A, Coutinho J, Ferreira G, Freitas I, Silvestre F, Justiça B. PMID: 11224498 [PubMed - indexed for MEDLINE]
- 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]
- Chronic eosinophilic leukaemia presenting with erythroderma, mild eosinophilia and hyper‐IgE: clinical, immunological and cytogenetic features and therapeutic approach. A case report.Publication . GRANJO, E.; LIMA, M.; LOPES, J.M.; DORIA, S.; ORFAO, A.; YING, S.; BARATA, L.T.; MIRANDA, M.; CROSS, N.C.; BAIN, B.J.Acta Haematol. 2002;107(2):108-12. Chronic eosinophilic leukaemia presenting with erythroderma, mild eosinophilia and hyper-IgE: clinical, immunological and cytogenetic features and therapeutic approach. A case report. Granjo E, Lima M, Lopes JM, Dória S, Orfão A, Ying S, Barata LT, Miranda M, Cross NC, Bain BJ. Department of Clinical Haematology, Hospital Geral de São João, Porto, Portugal. elisagranjo@netc.pt Abstract A 23-year-old, white male metallurgist presented with pruritic erythematous maculo-papules over the trunk and upper limbs and 6 months later developed erythroderma, eosinophilia and multi-organ dysfunction. A diagnosis of chronic eosinophilic leukaemia was made on the basis of myeloproliferative involvement of both peripheral blood and bone marrow, associated with eosinophilic differentiation and a t(5;12)(q33;p13) translocation. The initial therapeutic approach was interferon alfa-2b plus cytosine arabinoside, for 13 months, followed by hydroxyurea plus vincristine. There was improvement of skin lesions, disappearance of eosinophilia and decrease of serum immunoglobulin E, towards normal values. Copyright 2002 S. Karger AG, Basel PMID: 11919392 [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
- Immunophenotype and TCR‐Vbeta repertoire of peripheral blood T‐cells in acute infectious mononucleosis.Publication . LIMA, M.; TEIXEIRA, M.; QUEIROS, M.L.; SANTOS, A.H.; GONCALVES, C.; CORREIA, J.; FARINHA, F.; MENDONCA, F.; SOARES, J.M.; ALMEIDA, J.; ORFAO, A.; JUSTICA, B.Blood Cells Mol Dis. 2003 Jan-Feb;30(1):1-12. Immunophenotype and TCR-Vbeta repertoire of peripheral blood T-cells in acute infectious mononucleosis. Lima M, Teixeira Mdos A, Queirós ML, Santos AH, Gonçalves C, Correia J, Farinha F, Mendonça F, Soares JM, Almeida J, Orfão A, Justiça B. Service of Clinical Haematology, Hospital Santo António, Porto, Portugal. mmc.lima@clix.pt Abstract Although a number of studies on the phenotypic changes that occur after T-cell activation have already been published, the specific immunophenotypic features of T-lymphocytes and the frequency at which TCR-variable region (TCR-V) restricted T-cell expansions occur "in vivo" during acute viral infection still remains to be established. We report on the immunophenotype and TCR-V repertoire of peripheral blood T-cells from 28 patients with acute infectious mononucleosis. Immunophenotypic studies were performed by flow cytometry using direct immunofluorescence techniques and stain-and-then-lyse sample preparation protocols with three- and four-colour combinations of monoclonal antibodies directed against a large panel of T- and NK-cell associated markers, activation- and adhesion-related molecules and TCR-Vbeta, -Vgamma and -Vdelta families. Nearly all patients (27/28) showed a massive expansion of CD8(+)/TCRalphabeta(+) T cells, the majority (>90%) of which displayed an immunophenotype compatible with T-cell activation: CD2(+high), CD7(+low), CD11a(+high), CD38(+high), HLA-DR(+high), CD28(+/-low), CD45RO(+high), CD45RA(-/+low), CD11b(-/+low), CD11c(+/-low), CD16(-), CD56(-), CD57(-), CD62L(-), CD94(-), CD158a(-), CD161(-), NKB1(-). Additionally, the levels of both CD3 and CD5 were slightly decreased compared to those found in normal individuals. Late-activation antigens, such as CD57, were found in small proportions of CD8(+)/TCRalphabeta(+) T-cells. Increased numbers of CD4(+)/TCRalphabeta(+) T-cells, TCRgammadelta(+) T-cells and NK-cells were also noticed in 17, 16 and 13 of the 28 cases studied, respectively. Evidence for activation of CD4(+)/TCRalphabeta(+) and TCRgammadelta(+) T-cells relied on changes similar to those described for CD8(+)/TCRalphabeta(+) although less pronounced, except for higher levels of both CD5 and CD28 in the absence of reactivity for CD11c on CD4(+)/TCRalphabeta(+) T-cells and higher levels of CD161 and CD94 on TCRgammadelta(+) T-cells. Small expansions of one or more TCR-Vbeta families accounting for 12 +/- 7% of either the CD8(+)/TCRalphabeta(+) or the CD4(+)/TCRalphabeta(+) T-cell compartment were found in 12 of 14 patients studied, whereas the distribution of the TCR-Vgamma and -Vdelta repertoires tested in 2 of the individuals with expanded TCRgammadelta(+) T-cells was similar to that observed in control individuals. The results presented here provide evidence for an extensive T-cell activation during acute viral infection and establish the immunophenotype patterns associated with this condition. PMID: 12667982 [PubMed - indexed for MEDLINE]
- 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
- Immunophenotypic characterization of normal blood CD56+lo versus CD56+hi NK‐cell subsets and its impact on the understanding of their tissue distribution and functional propertiesPublication . LIMA, M.; TEIXEIRA, M.A.; QUEIROS, M.L.; LEITE, M.; SANTOS, A.H.; JUSTICA, B.; ORFAO, A.Blood Cells Mol Dis. 2001 Jul-Aug;27(4):731-43. Immunophenotypic characterization of normal blood CD56+lo versus CD56+hi NK-cell subsets and its impact on the understanding of their tissue distribution and functional properties. Lima M, Teixeira MA, Queirós ML, Leite M, Santos AH, Justiça B, Orfão A. Service of Clinical Hematology, Unit of Cytometry, Hospital Geral de Santo António, Porto, Portugal. mmc.lima@clix.pt Abstract In the present study we have compared the immunophenotypic characteristics of the CD56+lo and CD56+hi NK-cell subsets in a group of normal healthy adults. Our results show that CD56+hi NK-cells display greater light-scatter properties than CD56+lo NK-cells at the same time they have higher levels of CD25 and CD122 IL-2 chains, together with a higher reactivity for HLA-DR and CD45RO and lower levels of CD45RA, supporting that, as opposed to the majority of the CD56+lo population, CD56+hi NK-cells might correspond to a subset of activated circulating NK-lymphocytes. Higher expression of the CD2 and CD7 costimulatory molecules found for the CD56+hi NK-cells would support their greater ability to respond to various stimuli. In addition, CD56+hi NK-cells expressed higher levels of several adhesion molecules such as CD2, CD11c, CD44, CD56, and CD62L compared to CD56+lo NK-cells, supporting a particular ability of these cells to migrate from blood to tissues and/or a potential advantage to form conjugates with target cells. Interestingly, CD56+lo and CD56+hi NK-cells showed a different pattern of expression of killer receptors that might determine different activation requirements for each of these NK-cell subsets. For instance, absence or low levels of CD16 expression might explain the lower antibody-dependent cytotoxicity activity of CD56+hi NK-cells. On the other hand, the virtual absence of expression of the CD158a and NKB1 immunoglobulin-like and the greater reactivity for the CD94 lectin-like killer receptors on CD56+hi in comparison to CD56+lo NK-cells might determine different MHC-class I specificities for both NK-cell subsets, a possibility that deserves further studies to be confirmed. PMID: 11778657 [PubMed - indexed for MEDLINE]
- 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]
- Philadelphia‐positive T‐cell acute lymphoblastic leukemia with polymyositis, migratory polyarthritis and hypercalcemia following a chronic myeloid leukemiaPublication . LIMA, M.; COUTINHO, J.; BERNARDO, L.; DOS ANJOS TEIXEIRA, M.; CASAIS, C.; CANELHAS, A.; QUEIROS, L.; ORFAO, A.; JUSTICA, B.Ann Hematol. 2002 Mar;81(3):174-7. Epub 2002 Jan 31. Philadelphia-positive T-cell acute lymphoblastic leukemia with polymyositis, migratory polyarthritis and hypercalcemia following a chronic myeloid leukemia. Lima M, Coutinho J, Bernardo L, dos Anjos Teixeira M, Casais C, Canelhas A, Queirós L, Orfão A, Justiça B. Department of Clinical Hematology, Hospital Geral de Santo António, Rua D Manuel II, s/n, 4099-001 Porto, Portugal. mmc.lima@clix.pt Abstract Transformation of chronic myeloid leukemia (CML) often results in acute myeloblastic or, less frequently, in precursor B-cell acute lymphoblastic leukemia (ALL). T-cell blast crisis is rare. Hypercalcemia has also been described as a rare complication of CML, but this usually occurs as a terminal event. Here we report a case of a 35-year-old woman who developed a CD4(+)/CD8(+) T-cell ALL 2 years after the diagnosis of a typical Ph(+) CML. Polymyositis and polyarthritis preceded by 4 months, and symptomatic hypercalcemia occurred just before blastic transformation, probably representing paraneoplastic manifestations of the disease. PMID: 11904747 [PubMed - indexed for MEDLINE]
- Reactive phenotypes after acute and chronic NK‐cell activationPublication . 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]