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Biomedical subjects

E Matutes

Publications and source records attributed to E Matutes.

At least 91 records · Page 5Linked to original sources
PubMed1998

Lymphopain, a cytotoxic T and natural killer cell-associated cysteine proteinase.

Through differential screening of established human leukaemia cell lines, we have identified and molecularly cloned lymphopain, a novel cysteine proteinase of the papain family. Lymphopain exhibits a remarkably restricted cellular pattern of expression, being predominantly expressed in cytotoxic T-lymphocytes and natural killer cells. The human lymphopain locus maps to chromosome 11q13, encodes a polypeptide of 376 amino acids and is conserved in the mouse. Both human and murine forms appear more closely related to protozoan papain-like enzymes than to other mammalian members of the papain family. The cellular distribution of lymphopain expression, together with the functional demonstration of lymphopain-associated proteinase activity in vitro, is suggestive of a role for lymphopain in immune cell-mediated, cell killing.

Amino Acid Sequence↗
PubMed1998

Detection of minimal residual disease in B-lineage acute lymphoblastic leukaemia by quantitative flow cytometry.

The clinical significance of detecting minimal residual disease (MRD) in B-lineage acute lymphoblastic leukaemia (ALL) was evaluated by quantitative flow cytometry using a combination of TdT with CD10 and CD19. 53 patients with B-cell precursor ALL were followed during and after completion of treatment (median follow-up 23 months). Nine patients relapsed and MRD had been detected in six of them, 5-15 weeks before relapse despite morphological complete remission. 43 patients remain in clinical remission and in none of these was MRD detected. Disease-free survival based on the detection of MRD by flow cytometry showed a statistically significant difference between both groups (P<0.0001). The absence of MRD correlates with a low relapse rate, whereas the presence of MRD predicted early relapse. This study has shown that flow cytometry can improve the morphologic assessment of bone marrow (BM) remission status in B-lineage ALL. The finding of < 5% blasts in BM aspirates did not correlate with 'true' remission in a proportion of cases as residual leukaemic blasts were detected by flow cytometry in nine samples from six patients. On the other hand, the presence of > 5% blasts assessed by morphology was not necessarily a feature of relapse in five patients as these cells were shown to have a phenotype identical to normal TdT-negative B-cell precursors. Quantitative flow cytometry was more informative than conventional morphology to assess remission status and showed a strong correlation with clinical outcome. This methodology is useful to define MRD in the majority of patients with B-lineage ALL and should be tested in prospective clinical trials.

Adult↗
PubMed1998

Prolonged disease-free survival in relapsed/refractory low-grade lymphoma treated with fludarabine: a report of four cases.

We report four patients with relapsed or refractory follicular (three) and lymphoplasmacytic (one) lymphoma who achieved complete remission (CR) with fludarabine (FDR) lasting from 3.2 to 6 years. One had stage III and three stage IV and were resistant to chlorambucil and/or anthracycline. FDR was well tolerated, the only complication being herpes zoster infection in three patients, which was controlled with aciclovir. One patient developed a gastric MALT lymphoma from a different clone than the follicular lymphoma. In conclusion, some patients with refractory low-grade lymphoma achieve long-term CR with FDR: therefore this agent may be considered as alternative to stem-cell transplantation.

Adult↗
PubMed1998

Levels of expression of CD19 and CD20 in chronic B cell leukaemias.

AIMS: To investigate whether the antigen levels of the B cell lineage markers CD19 and CD20 can distinguish between normal and neoplastic B cells or characterise distinct expression patterns among the chronic B cell leukaemias. METHODS: Peripheral blood cells from 70 patients with B cell disorders and 17 healthy donors were analysed by quantitative flow cytometry. Direct immunofluorescence staining was performed with phycoerythrin conjugated CD19 and CD20 monoclonal antibodies. Standard microbeads with different capacities to bind mouse immunoglobulins were used to convert the mean fluorescence intensity (MFI) values into number of antigen molecules/cell, expressed as antibody binding capacity (ABC). RESULTS: CD19 and CD20 ABC values in leukaemic B cells differed from those of normal blood B lymphocytes. The results identified distinct profiles of CD19 and CD20 expression in the various types of B cell leukaemias. In all leukaemias studied except hairy cell leukaemia (HCL), CD19 expression was significantly lower than the mean (SD) value in normal B cells (22 (7) x 10(3) molecules/cell), as follows: chronic lymphocytic leukaemia (CLL), 13 (7) x 10(3); B prolymphocytic leukaemia (B-PLL), 16 (9) x 10(3); splenic lymphoma with villous lymphocytes (SLVL), 15 (11) x 10(3); mantle cell lymphoma (MCL), 10 (7) x 10(3). In HCL there was strong CD19 expression (38 (16) x 10(3)). In contrast, the level of expression of membrane CD20 was higher than the mean (SD) value in normal B cells (94 (16) x 10(3) molecules/cell) in MCL (123 (51) x 10(3)); B-PLL (129 (47) x 10(3)); SLVL (167 (72) x 10(3)); and HCL (312 (110) x 10(3)); while it was significantly lower (65 (11) x 10(3)) in CLL compared with normal B cells and the other B cell leukaemias. CONCLUSIONS: Quantitative determination of CD19 and CD20 may provide useful diagnostic information for the study of B lymphoproliferative disorders.

Antigens, CD19↗
PubMed1998

T-cell Prolymphocytic Leukemia.

BACKGROUND: T-cell prolymphocytic leukemia (T-PLL) is a post-thymic T-cell malignancy with aggressive clinical course. Although T-PLL has been referred to under different designations, it is a distinct clinico-biological entity and should be distinguished from other T-cell disorders. METHODS: The literature on T-PLL is reviewed. Experience on the clinical and laboratory features, differential diagnosis, and therapy on a large series of T-PLL patients is presented. RESULTS: T-PLL affects adults and occurs more frequently in men. The principal disease characteristics are organomegaly, skin lesions, and a raised lymphocyte count. Immunological markers show a post-thymic T-cell phenotype (TdT- CD2+ CD5+ CD3ñ) with strong expression of CD7. A CD4+ CD8- phenotype is seen in two thirds of cases. CD4 and CD8 are coexpressed in 25%, and a CD4- CD8+ phenotype is rare. Cytogenetics show a recurrent abnormality inv(14)(q11;q32) that is always associated to other aberrations (particularly iso8q or trisomy 8). Differential diagnosis between T-PLL and other T-cell malignancies is based on a constellation of clinical and laboratory features. Generally, T-PLL patients are refractory to the therapy used in lymphoid disorders. Median survival is short but is improving with the use of 2'-deoxycoformycin and the humanized monoclonal antibody, anti-CDw52 (Campath-1H). CONCLUSIONS: T-PLL is a distinct T-cell disorder with characteristic clinical and laboratory features and a poor prognosis. A precise diagnosis of this disease is important in determining patient management and treatment.

Journal Article↗
PubMed1998

Signet-ring cells in a Waldenström's Macroglobulinaemia.

A case of signet-ring cell lymphoma affecting bone marrow is reported. The patient was diagnosed as Waldenström's Macroglobulinaemia on the basis of clinical and laboratory features including morphology, immunohistochemistry and gene rearrangement studies. Light microscopy examination showed cells contained large globular inclusions (signet-ring cells) that stained for kappa immunoglobulin light chain by immunohistochemistry. In addition, the neoplastic cells expressed the common leukocyte antigen CD45 and the B cell marker CD19. This to the best of our knowledge is the first report of a patient with Waldenström's Macroglobulinaemia with the presence of vacuolated signet ring- cells in the bone marrow. Differential diagnosis arises with non-haemopoietic tumours and this needs to be based on specific immunostaining. Tumours and this need to be based on specific immunostaining.

Aged↗
PubMed1998

bcl-2 expression in plasma cells from neoplastic gammopathies and reactive plasmacytosis: a comparative study.

BACKGROUND AND OBJECTIVE: bcl-2 oncoprotein plays a major physiological role in hemopoietic and non-hemopoietic cells by preventing apoptosis (programmed cell death). Disregulation of this process may be important in oncogenesis and the response to treatment of patients with different hematological malignancies. We have investigated the levels of bcl-2 expression in plasma cells from patients with reactive plasmacytosis (RP), monoclonal gammopathy of unknown significance (MGUS) and multiple myeloma (MM), correlating the bcl-2 expression and clinico-biological features in MM patients. DESIGN AND METHODS: The percentage of bcl-2 (+) plasma cells and levels of bcl-2 protein expression were investigated in 73 patients at diagnosis. Immunofluorescence and immunoenzymatic methods were applied using McAb against bcl-2 protein, and the intensity of protein expression was assessed by both the mean channel fluorescence intensity (MFI) and semiquantitative methods. To evaluate the intensity of bcl-2 expression in proliferating plasma cells, sequential double immunoenzymatic staining with McAb Ki-67 and bcl-2 was applied in 10 patients with MM. Correlations between bcl-2 expression and the clinico-biological features in MM patients were also studied. RESULTS: The proportion of bcl-2 (+) plasma cells was significantly higher in MGUS and MM than in RP (p < 0.001). The intensity of bcl-2 expression in plasma cells (assessed by MFI) was significantly different between all groups studied (p < 0.0001). RP showed lower expression than MGUS and MM patients. MM stage III patients demonstrated higher bcl-2 expression values than MGUS (p < 0.01). According to the proportion of plasma cells expressing Ki-67, patients with a proliferative index (Ki-67+) > 4% showed lower bcl-2 expression than patients with proliferative index < 4% (p < 0.05). Immunocytochemistry showed that plasma cells from RP had a lower intensity of bcl-2 expression than MM (p < 0.001), and double immunostaining Ki-67/bcl-2 demonstrated that the majority of proliferating plasma cells had weak bcl-2 expression. There was no correlation between bcl-2 expression and clinico-biological parameters, response to therapy or overall survival in MM patients. INTERPRETATION AND CONCLUSIONS: Globally, the number of bcl-2 (+) plasma cells and the intensity of protein expression in neoplastic gammopathies are significantly higher than in reactive plasmacytosis and bcl-2 levels tend to increase with disease stage. bcl-2 may be relevant to the pathogenesis of malignant gammopathies, prolonging the survival of plasma cells by preventing apoptosis and increasing the chance of acquiring additional gene defects. bcl-2 expression could also contribute to the resistance to chemotherapy observed in MM disease.

Adult↗
PubMed1998

Trisomy 12 and lymphoplasmacytoid lymphocytes in chronic leukemic B-cell disorders.

BACKGROUND AND OBJECTIVE: Although the finding of trisomy 12 in B-cell malignancies has been extensively documented especially in B-CLL, little is known about the clonal involvement of different tissues and there are few sequential studies documenting the development of trisomy 12 during the course of the disease. The aim of this study was, therefore, to: 1) ascertain the prevalence of trisomy 12 by FISH; 2) correlate the findings of trisomy 12 with hematologic and clinical features; 3) study the trisomy 12 positive clone during the course of the disease, and 4) compare findings of trisomy 12 in different tissues. DESIGN AND METHODS: This a study of an unselected population of 118 patients with CLL or other B-cell disorders in leukemic phase from a defined geographic area. Trisomy 12 was detected by FISH. RESULTS: Trisomy 12 was found in 18 patients (15%). The aberration was significantly more common in morphologically atypical CLL (aCLL) (24%) and CLL/PL (67%) compared to typical CLL (2%) (p < 0.001). aCLL cases had predominantly lymphocytes with lymphoplasmacytoid features. Sequential studies of peripheral blood showed an increase in the proportion of trisomic cells during the observation time, mostly associated with disease progression. None of the initially trisomy 12 negative patients acquired the aberration during follow-up. The percentage of lymphocytes exhibiting trisomy 12 was significantly (p < 0.05) higher in the bone marrow than in peripheral blood. INTERPRETATION AND CONCLUSIONS: Trisomy 12 might define a distinct disease entity with atypical lymphocytes in chronic leukemic B-cell disorders.

Aged↗
PubMed1997

p53 abnormalities in B-cell prolymphocytic leukemia.

B-cell prolymphocytic leukemia (B-PLL) is an aggressive disorder of mature B cells with distinct clinical and pathologic features. To determine the incidence of abnormalities of p53, we analyzed 19 cases of B-PLL by DNA blot to assess loss of heterozygosity (LOH) at 17p13.3, by immunocytochemistry to assess p53 expression, and by direct DNA sequencing of polymerase chain reaction-amplified exons 5 to 9 of the p53 gene. LOH was detected in 10 of 19 (53%) cases, p53 expression was detected in 8 of 17 (47%), and p53 mutations were detected in 10 of 19 (53%) cases. The pattern of mutations was distinct from that observed in other B-cell malignancies. Six cases exhibited missense mutations; 4 were transversions and 2 were transitions. The G:C --> A:T transition at cathepsin G dinucleotides commonly reported in p53 mutations in chronic lymphocytic leukemia (CLL) and other hematologic malignancies was observed in only 1 case of B-PLL. Three cases exhibited deletions (ranging from 3 to 35 bp in length) and one case exhibited a 2-bp insertion. In 1 case, a 27-bp deletion resulted in the expression of a p53 protein lacking 9 amino acids from the DNA binding region. All samples with p53 mutation showed loss of germline p53 sequences. However, 3 of 10 showed no LOH by Southern blot, indicating a localized deletion around the p53 locus at 17p13.1. Five of the 10 cases with p53 mutation exhibited detectable p53 expression, including 4 cases with p53 missense mutation and 1 case with deletion. Two of 7 cases with no detectable mutation of p53 nevertheless overexpressed p53. Therefore, there was no correlation between protein expression and p53 mutation in B-PLL. Our data indicate that the overall abnormalities of p53 occurred in 14 of 19 (75%) cases of B-PLL. The frequency of p53 mutation (53%) in B-PLL is the highest reported in B-cell malignancies and may be responsible for the frequent resistance to therapy of this disease. In addition, the pattern of p53 mutation was different from that observed in CLL and other hematologic malignancies and may indicate that a distinct pathogenic mechanism operates in B-PLL.

Aged↗
PubMed1997

Quantification of P-glycoprotein in chronic lymphocytic leukemia by flow cytometry.

The P-glycoprotein (P-gp) was investigated in 40 patients with chronic lymphocytic leukemia by immunological, functional and quantitative assays. The proportion of positive cases with the anti-Pgp McAb UIC2 was 30% and increased to 64% after neuraminidase treatment (p = 0.002). Fifty-six per cent of cases were positive with the functional test with rhodamine 123 and verapamil. A negative correlation was found between the number of cells stained with the McAb and the functional test (p = 0.006). The mean of P-gp molecules was 2509 +/- 2805 molecules per cell; these values were higher than in the control K562 cell line in the majority of cases. The number of positive cases and P-gp molecules were higher in treated than in untreated patients (p = 0.01 and 0.07). There were no significant differences with respect to response to treatment, but a higher number of P-gp molecules was found in non-responders. When the results of the functional test were put together with the quantification assay this allowed the detection of 71% non-responders. Our findings suggest that quantification of the P-gp could be of value in the assessment of possible drug resistance in CLL.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Two unbalanced translocations, t(12;22)(p13;q11) and t(12;?)(p13;?), in an aggressive chronic B-cell leukemia: TEL gene analysis using FISH.

The translocation t(12;22)(p13;q11) has been consistently described in myeloid malignancies and shown to result from a fusion between the TEL and MN1 genes. Previously described deletions of 12p in acute lymphoblastic leukemias have been recently shown to harbor undetected translocations involving the TEL gene at 12p13. We document a case of an aggressive chronic B-cell leukemia whose cells had trisomy 12 and two unbalanced translocations involving 12p13, including a t(12;22)(p13;q11) as shown by conventional cytogenetics and fluorescence in situ hybridization (FISH). The 12p13 breakpoint of the t(12;22)(p13;q11) was telomeric to the TEL gene, and the second unbalanced translocation with breakpoint 12p13 resulted in the deletion of TEL. This case demonstrates that TEL gene deletions may be relevant in cases of mature B-lymphoproliferative diseases.

Chromosomes, Human, Pair 12↗