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Biomedical subjects

E Matutes

Publications and source records attributed to E Matutes.

At least 145 records · Page 8Linked to original sources
PubMed1996

Correlation of trisomy 12 with proliferating cells by combined immunocytochemistry and fluorescence in situ hybridization in chronic lymphocytic leukemia.

Conventional G-banding and fluorescence in situ hybridization (FISH) were performed on peripheral blood samples of 340 consecutive untreated cases of chronic lymphocytic leukemia (CLL) for the detection of trisomy 12 and other chromosome abnormalities. These findings were correlated with the proliferative activity of CLL lymphocytes assessed by the monoclonal antibody Ki-67. Cytogenetic analysis displayed a normal karyotype in 131 (38.5%) cases, trisomy 12 in 68 (20%), 31 by G-banding and an additional 37 cases by FISH, other clonal abnormalities in 47 (14%), and no metaphases in 94 (27.5%). The percentage of Ki-67-positive cells was significantly higher in cases with trisomy 12 (4.1 +/- 4.48) than in cases with a normal karyotype (1.5 +/- 2.0), those with other clonal abnormalities (1.35 +/- 1.37) and cases with no metaphases (1.14 +/- 1.6) (P< 0.0001). Cases with trisomy 12 were associated with more advanced clinical stage, atypical morphology and a higher percentage of Ki-67+ve cells than cases lacking trisomy 12 (P< 0.0001). Although there was no direct correlation between the percentage of trisomic and proliferating cells, the combination of immunocytochemistry and FISH showed that most Ki-67-positive cells were trisomic for chromosome 12. Our results suggest that the association of trisomy 12 with a higher proliferative activity supports the view that this abnormality is a secondary event associated with disease progression in CLL.

Adult↗
PubMed1996

Expression of the immunoglobulin-associated protein B29 in B cell disorders with the monoclonal antibody SN8 (CD79b).

We studied the expression of the immunoglobulin-associated membrane protein B29 in 499 cases of chronic B cell diseases using the monoclonal antibody SN8 (CD79b). SN8 was positive in 5% (17/330) of chronic lymphocytic leukemia (CLL) and 100% (15/15) of B prolymphocytic leukemia. The expression of B29 in other B cell disorders was, as a rule, significantly higher than in CLL. Two thirds of non-Hodgkin's lymphomas in leukemic phase were SN8 positive, including lymphoplasmacytic (45%), follicular (83%), mantle cell (92%) and splenic lymphoma with villous lymphocytes (74%) while only 25% of hairy cell leukemias were SN8 positive. Within CLL, 2.3% of typical cases were SN8+ while 16% of cases with atypical morphology and an increased number of prolymphocytes were SN8+. Our results suggest a useful role for SN8 in the immunophenotypic differentiation of B cell disorders as a marker for non-CLL diseases. The analysis of B29 expression may throw light into the structure of the B cell antigen receptor in B cell malignancies while the distinctive reactivity profile of SN8 has direct applications to diagnosis.

Antibodies, Monoclonal↗
PubMed1996

[Immunophenotype. Clinical and laboratory features of acute lymphoblastic leukemia in Chile. Study of 500 children and 131 adults].

We describe the clinical features and immunophenotype of 500 children and 131 adults with acute lymphoblastic leukemia (ALL), diagnosed between 1984 and 1993. Cases were classified, according to immunophenotype in B-cell ALL with three subtypes (pro-B or null, common and B) and T-cell ALL. Among children, common ALL accounted for 74% of cases and pro-B all was more common in children of less than one year (14%). B ALL was observed in 2% of children. Ten percent of children, mostly males, had T-cell ALL. The third part of these children had high leukocyte counts and a mediastinal mass. Children from Mapuche origin, compared with Caucasian children had a lower proportion of common ALL (36 and 74% respectively) and a higher proportions of T-cell ALL (41 and 10% respectively). Among adults common ALL was the most common phenotype (72%) followed by T-cell ALL (15%), pro-B ALL (11%) and B-cell ALL (2%). There was a lower incidence of children with common ALL with positive cytoplasmic immunoglobulin compared to North American or European studies (2 and 15-33% respectively) and a higher proportion of adults with common ALL compared with pro-B cell ALL, in contrast to European studies that show a higher proportion of patients with pro-B cell ALL. No other immunophenotypic, clinical or laboratory differences were observed with ALL from developed countries. It is concluded that the immunophenotyping of ALL allows a more precise diagnosis of this disease.

Adolescent↗
PubMed1995

T-cell malignancies in Brazil. Clinico-pathological and molecular studies of HTLV-I-positive and -negative cases.

T-cell malignancies in Brazil have a high seroprevalence rate of HTLV-I antibodies. We have analyzed the disease features in 188 Brazilian patients with a T-cell disorder. These included 40 with T-lymphoblastic leukaemia or lymphoma (T-ALL/T-LbLy) and 148 with mature T-cell diseases: 5 T-prolymphocytic leukaemia, 53 adult T-cell leukaemia/lymphoma (ATLL), 54 cutaneous T-cell lymphomas, 29 pleomorphic T-cell lymphomas and 7 large granular lymphocyte leukaemia. The diagnosis was based on clinical, morphological and immunological features and HTLV-I serology. ATLL in Brazil has the same diseases features as in other endemic regions, the only apparent differences being: age, Brazilian patients being younger than Japanese, and ethnic grouping, one third of Brazilians being white Caucasians of European descent. We applied a scoring system based on the presence or absence of typical features associated with ATLL; hypercalcaemia, cell morphology, immunophenotype, histopathology and HTLV-I status, to see whether it may help in diagnosing cases of ATLL. All had high scores, whereas all other T-cell diseases scored low. Only 5 ATLL cases were HTLV-I-negative by serology, but they had otherwise typical features of ATLL, and their cells did not have HTLV-I proviral sequences by DNA analysis. Such cases suggest that ATLL may develop in a minority of individuals living in regions where it is endemic, without evidence of HTLV-I infection, and that other factors may contribute to the pathogenesis of the disease.

Adolescent↗
PubMed1995

Cytogenetic abnormalities in the leukemic phase of non-Hodgkin lymphoma.

We have carried out chromosome analysis in a series of 16 non-Hodgkin Lymphoma (NHL) cases in leukemic phase. The diagnoses in these patients based on histology and immunologic markers were as follows: follicular lymphoma (FL), 3 cases; mantle cell lymphoma (Mc), 4 cases; lymphoplasmacytic lymphoma (LPL), 8 cases, and large cell lymphoma, 1 case. We have shown that the t(14;18), t(11;14), and trisomy 12 retained their subtype association with FL, Mc, and LPL, respectively, as in their nonleukemic counterparts with one case of FL showing t(1;19)(q23;p13). Among the four LPL cases without trisomy 12, one case each showed t(12;14)(q13;q32), trisomy 14, t(1;3)(p34;q21), and del(3)(q21). The t(1;19) and t(12;14) may represent rare events in FL and LPL, respectively, and may be uniquely associated with the leukemic phase. The breakpoint 14q32 was the most common single breakpoint involved, sometimes involving both chromosome 14 homologues depicting its association with primary and secondary genetic events in the disease progression. In addition to the main abnormalities, we have shown additional complex abnormalities in 14 of 16 cases. Among these, chromosome 3 was the most commonly involved, affecting the short or long arm or the whole chromosome; 5 of the 16 cases involved breakpoint 3q21. The high incidence of additional abnormalities in these NHL in leukemic phase suggest an association with the development of leukemia and progression of the disease.

Adult↗
PubMed1995

Hepatosplenic gamma delta T-cell lymphoma. A distinctive aggressive lymphoma type.

The T-cell receptor (TCR) expressed on the surface of most T-lymphocytes is of alpha beta type, and only a minority bear the gamma delta-TCR. Similarly, postthymic T-cell lymphomas rarely express gamma delta-TCR. Hepatosplenic gamma delta T-cell lymphoma is an uncommon entity that has so far not been widely recognized. We report one such case that has been comprehensively studied by multiple modalities and showed the unique occurrence of leukemic picture at presentation. The 39-year-old man presented with fever, marked weight loss, and massive splenomegaly. Peripheral blood showed thrombocytopenia and a white cell count of 5.8 x 10(9)/l, with 66% medium-sized lymphoid cells that had a round or folded nucleus, condensed chromatin and a moderate amount of pale blue cytoplasm. Splenectomy was performed and histologic examination of the spleen, bone marrow, liver, and abdominal lymph nodes demonstrated lymphoma infiltration with a predominantly sinusoidal pattern. Immunohistochemical studies of the lymphoma cells showed a T-cell phenotype: CD2+ CD3+ CD5+ CD7+ gamma delta-TCR+ alpha beta-TCR- CD56+ CD4- CD8- CD16- CD57-. Cytogenetic studies showed complex clonal chromosomal abnormalities of 44,X, -Y, -11, -22, + mar in 3/16 cells. Rearrangement of the TCR gamma chain gene was demonstrated by polymerase chain reaction; the TCR beta chain gene was partially chain reaction; the TCR beta chain gene was partially rearranged. The patient did not respond to single agent chemotherapy, but achieved clinical remission with combination chemotherapy. Based on the available data in the literature, hepatosplenic gamma delta T-cell lymphoma exhibits distinctive clinicopathologic features, and probably represents the neoplastic counterpart of splenic gamma delta T-lymphocytes. This disease is associated with a poor prognosis and usually relapses despite initial response to chemotherapy.

Adult↗
PubMed1995

Cutaneous infiltration in T-cell prolymphocytic leukaemia.

T-cell prolymphocytic leukaemia (T-PLL) is an aggressive leukaemia accounting for over 30% of all mature T-cell malignancies. We describe the clinical manifestations and histology of cutaneous involvement in a series of 92 patients with T-PLL. Of the 92 patients, 26 (28%) had cutaneous involvement, and in 23 this was present at the time of the diagnosis of the leukaemia. Skin manifestations included a diffuse infiltrated erythema, infiltration localized to the face and ears, nodules and erythroderma. Histology showed a perivascular and periappendageal dermal infiltrate of lymphoid cells with the morphology of prolymphocytes. An early skin biopsy in these patients should help to reveal the underlying diagnosis.

Adult↗
PubMed1995

Quantitative flow cytometry can distinguish between normal and leukaemic B-cell precursors.

The immunological detection of minimal residual disease in B-lineage acute lymphoblastic leukaemia (ALL) has been hampered by the fact that the leukaemic cells represent the malignant counterparts of normal haemopoietic precursors expressing terminal deoxynucleotidyl transferase (TdT), CD10 and CD19. We have used quantitative double-labelling flow cytometry with standard fluorescent beads to convert the mean fluorescence to the number of antigen molecules per cell. The number of TdT, CD10 and CD19 molecules per cell was determined in normal B-cell precursors from 22 healthy donors and eight regenerating marrows from patients with various malignancies and in 20 cases of B-lineage ALL. In normal bone marrow we characterized two different B-cell populations: TdT+/CD10+/CD19+ and TdT-/CD10+/CD19+. We demonstrated a major difference in the level of expression of TdT, CD10 and CD19 between normal bone marrow and B-lineage ALL blasts. Normal TdT+ precursors have significantly higher number of TdT (> 100 x 10(3)) and lower number of CD10 (< 50 x 10(3)) and CD19 (< 10 x 10(3)) molecules per cell than B-lineage ALL blasts (< 100, > 50, > 10 x 10(3) molecules per cell respectively); these differences were statistically highly significant. Furthermore, regenerating marrows had a significantly higher percentage of B-cell precursors than healthy donors. This increase was at the expense of the TdT-/CD10+/CD19+ population which, in the context of B-lineage ALL, could be wrongly interpreted as evidence of relapse if TdT is not included in the analysis. Therefore the quantitative analysis of TdT combined with CD10 and CD19 may allow a clear distinction between normal precursors and minimal residual leukaemia in B-lineage ALL and avoid the pitfall of misinterpreting regenerating B-cells as evidence of relapse.

Adolescent↗
PubMed1995

The first report of familial adult T-cell leukaemia lymphoma in the United Kingdom.

We describe two siblings who developed adult T-cell leukaemia lymphoma (ATLL) within 4 years. Both were black of Afro-Caribbean extraction, but one had been born in the United Kingdom and had visited the Caribbean only once. Both patients were HTLV-1 seropositive, as was their mother; their father and brother were negative. The older sibling had the lymphoma form of ATLL, whilst the younger had chronic ATLL. The former was unresponsive to chemotherapy and died of progressive disease; the latter experienced transient responses to various treatments and is alive 5 years after presentation. Immunophenotyping showed a CD4+, CD25+ phenotype; Southern blot demonstrated a monoclonal integration of HTLV-I in the tissues involved. This report, of the first familial ATLL in the U.K., supports the suggestion of transmission of HTLV-I from mother to child and documents the development of ATLL in second-generation Caribbean immigrants.

Adult↗
PubMed1995

Circulating Ki67 positive lymphocytes in multiple myeloma and benign monoclonal gammopathy.

AIMS: To estimate the proportion and nature of the proliferating (Ki67+) circulating lymphocytes in a series of patients with multiple myeloma and monoclonal gammopathy of unknown significance (MGUS) and to correlate this with other clinical and laboratory parameters, using blood from healthy adults as a control. To investigate the extent to which the B and T lymphoid components are involved in progression and/or control of disease. METHODS: Blood lymphocytes from 15 patients with multiple myeloma, 10 patients with MGUS and 10 healthy adults were analysed using a sequential double immunoenzymatic staining technique. Antibodies directed against Ki67 were used to detect cells in cycle, CD3, CD4, and CD8 to identify T cells, HLA-Dr as a marker for B cells and activated T cells, and CD11b as a marker for natural killer cells. Polyclonal antibodies directed against the kappa and lambda immunoglobulin light chains were also used to detect B cells. RESULTS: The proportion of proliferating (Ki67+) lymphocytes was significantly higher in patients with multiple myeloma (6.8 +/- 2.6) and MGUS (3.5 +/- 1.1) compared with the normal controls (1.69 +/- 0.3); this was also true when multiple myeloma and MGUS cases were compared. In multiple myeloma and MGUS over 50% of the Ki67+ cells were activated T lymphocytes (CD3+/HLA-Dr+); a minority (11%) were non-clonal B lymphocytes. In contrast to controls (6.7 +/- 1.9), in patients with multiple myeloma and MGUS the proportion of proliferating T cells expressing CD8 (23.6 +/- 12.5 and 15.3 +/- 7.7, respectively) and CD11b (13 +/- 8.7 and 11.6 +/- 3.9, respectively) was higher. In multiple myeloma there was a positive correlation between the proportion of Ki67+ lymphocytes, beta-2-microglobulin concentrations and disease stage. CONCLUSIONS: Although the number of patients investigated is small, this study suggests that Ki67 expression in blood lymphocytes from patients with multiple myeloma may be a good prognostic indicator for aggressive disease and may help to distinguish multiple myeloma from MGUS. The activated proliferating T cells in these diseases may represent an immunological reaction against the tumour.

Adult↗
PubMed1995

HTLV-I positive progressive spastic paraparesis (TSP) associated with a lymphoid disorder in three Chilean patients.

We describe the clinical and laboratory features in three Caucasian Chilean patients with tropical spastic paraparesis (TSP) associated with/or preceded by a lymphoproliferative disorder involving cutaneous lesions and localised lymphadenopathy. The neurological symptoms and signs were characteristic of TSP and CSF examination revealed the presence of oligoclonal bands. All three patients had a moderate leucocytosis (10-14 x 10(9)/l) with eosinophilia and a minority (2-4%) of circulating atypical polylobed or ATLL-like lymphocytes. Lymph node histology showed a diffuse pattern of infiltration (1 case) and marked expansion of the paracortical zone with convoluted lymphocytes and immunoblasts (2 cases). Skin biopsy demonstrated a dermal lymphoid infiltration with epidermotropism. Antibodies to HTLV-I were detected in the serum and CSF in the three patients and Southern blot analysis of peripheral blood mononuclear cells showed a monoclonal integration of HTLV-I proviral DNA in one case whereas in the two others the pattern was indicative of low level polyclonal integration. All three patients were treated with prednisolone and one with PUVA with transient partial response on the skin and neurological manifestations. Two patients died months to 5 years from presentation and the other is alive 12 years from diagnosis with active neurological and skin disease. The simultaneous occurrence of HTLV-I associated TSP with smouldering ATLL and a cutaneous ATLL or pre-leukaemic form is discussed.

Adult↗
PubMed1995

Immunoblastic transformation of a Sezary syndrome in a black Caribbean patient without evidence of HTLV-I.

We describe an unusual case of Sezary syndrome which transformed into a large T-cell non Hodgkin's lymphoma (immunoblastic) in a black man of Caribbean descent with negative HTLV-I serology and no evidence of HTLV-I infection by DNA analysis using sensitive techniques. The disease presented as a small-cell Sezary syndrome and transformed in an inguinal lymph node one year from diagnosis. Immunological markers in the small and large cells showed a mature T-cell phenotype CD4+, CD8- with expression of T-cell activation markers and a high proliferative rate. Ultrastructural analysis confirmed small Sezary cells with serpentine nucleus in the peripheral blood and immunoblasts in the lymph node. Cytogenetics demonstrated complex clonal chromosome abnormalities with involvement of 7q35, the locus for the beta chain of the T-cell receptor (TCR). Southern-blot analysis showed the same rearrangement of the TCR beta, gamma, delta chain genes in lymph node and peripheral blood cells. Antibodies to HTLV-I were not detected in the serum by ELISA and particle agglutination (PA) nor HTLV-I specific sequences were demonstrated by nested polymerase chain reaction with primers to the envelope proteins, LTR and tax/rex of HTLV-I in both tissues, blood and lymph node. The disease had an aggressive course and was refractory to therapy; the patient died of progressive disease 28 months from presentation. Two unusual features characterised this patient's illness: immunoblastic transformation of a Sezary syndrome in a patient of Afro-Caribbean origin without evidence of HTLV-I DNA sequences and negative HTLV-I serology and the atypical lymph node histology resembling ATLL.

Base Sequence↗
PubMed1995

Expression of c-myc oncoprotein in chronic T cell leukemias.

T cell clones in patients with ataxia telangiectasia (AT) and T cell prolymphocytic leukemia (T-PLL) have identical chromosome abnormalities, namely inv(14)(q11q32), t(14;14)(q11;q32) and t(X;14)(q27;q11). In T-PLL and AT developing T cell leukemia, the above abnormalities occur frequently together with trisomy for 8q. We postulated that the additional abnormalities of chromosome 8, where the c-myc oncogene is mapped to 8q24, may play a role in the development of overt leukemia. DNA analysis using the CD1A c-myc probe did not reveal rearrangements of the c-myc gene by Southern blotting. We have used a monoclonal antibody for the c-myc protein to investigate the level of expression in 11 patients with T-PLL and two with Sezary cell leukemia and compared it with levels seen in normal lymphocytes. Significantly higher levels were observed in patients compared with controls (P < 0.0001). The highest levels of c-myc were seen in eight cases with trisomy for 8q resulting from an i(8q). One patient was investigated before and after treatment. In the active state, c-myc showed a level of 64.36 units (range 20-200). After treatment a residual population of malignant cells showed a c-myc level of 155 (range 90-280). This study suggests that the increased expression of c-myc as a result of trisomy for 8q may have a role in the pathogenesis of de novo T-PLL and T cell leukemia supervening AT and that there may be a correlation between c-myc levels and resistance to therapy.

Adult↗
PubMed1995

Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL).

Criteria for the immunological classification of acute leukemias are proposed by a recently established European group designated EGIL. The main aims of EGIL are to establish guidelines for the characterization of acute leukemias based on marker expression and provide a uniform basis for the diagnosis of the various types of these hemopoietic malignancies which should be helpful for future multinational clinical and laboratory investigations. Within the two major types (B and T cell lineage) of acute lymphoblastic leukemia (ALL), several groups are delineated according to the degree of cell differentiation. Within the acute myeloid leukemias (AML), only three subtypes as defined by the FAB classification: M0-AML, M6-AML and M7-AML, can be unequivocally defined by immunological markers; prospective studies are undertaken to see whether characteristic immunological profiles are associated with particular AML subtypes defined by specific cytogenetic abnormalities. Criteria for the definition of biphenotypic acute leukemia (BAL) are devised and a scoring system is outlined aimed to distinguish BAL from those acute leukemias with expression of a marker from another lineage. In addition, an uncommon subset of acute leukemias with no evidence of lymphoid or myeloid differentiation is recognized and the useful panel of markers to investigate and establish the cell nature of the acute leukemias is outlined. EGIL will focus in the future on testing the reproducibility of the proposed guidelines, particularly those for BAL, assessing their clinical value within a framework of multicentric trials and setting up uniform methodological criteria.

Acute Disease↗
PubMed1995

High degree of myeloid differentiation and granulocytosis is associated with t(8;21) smoldering leukemia.

The t(8;21) is a frequent chromosome abnormality in acute myeloid leukemia (AML), particularly associated with M2 of the French-American-British (FAB) classification, but also found in a few patients with myelodysplastic syndrome (MDS). The two genes involved in the t(8;21) have been recently isolated and the cDNA of the AML1/ETO fusion gene identified. We have investigated a series of AML and MDS patients by a reverse transcriptase-polymerase chain reaction (RT-PCR) and analyzed the clinical and laboratory features of leukemia with t(8;21). The t(8;21) was only found in a subset of M2, which had the clinical and hematological features distinct from those M2 without t(8;21). M2 with t(8;21) was associated with a significantly higher myeloid differentiation and with a good response to chemotherapy. Moreover, among the patients with refractory anemia with excess of blasts in transformation (RAEB-T) the t(8;21) was also significantly associated with a higher myeloid differentiation and a good response to chemotherapy. M2 patients with t(8;21) could be distinguished on a number of hematological parameters, eg white blood cell count and percentage of bone marrow myeloblasts and promyelocytes, from RAEB-T carrying the t(8;21). Based on these findings we suggest that leukemia patients carrying t(8;21) can be grouped into two types; overt acute myeloid leukemia (M2) and smoldering or slowly evolving myeloid leukemia.

Adolescent↗
PubMed1995

Differential TdT expression in acute leukemia by flow cytometry: a quantitative study.

Terminal deoxynucleotidyl transferase (TdT) has long been considered a diagnostic marker for acute lymphoblastic leukemia. Reports of TdT-positive cells in acute myeloid leukemia have lately questioned its diagnostic value. TDT has been detected mainly by microscopy methods: immunofluorescence and immunocytochemistry. The aim of this study was to reevaluate the diagnostic importance of TdT in acute leukemia by using flow cytometry with a method that allows quantitative analysis. Fifty-eight cases of acute leukemia were studied and TdT expression was quantified using calibrated fluorescent beads. The highest TdT values were found in B lineage acute lymphoblastic leukemia (ALL) while acute myeloid leukemia (AML) had the lowest values, even in cases with a high percentage of TdT-positive cells. Biphenotypic leukemia had intermediate values between B-lineage and T-lineage acute leukemia. The difference between these groups was statistically significant (P < 0.0001). The TdT assay by flow cytometry was more precise than immunocytochemistry because it recognizes quantitative differences between ALL and AML. It is also valuable in better defining the maturation stages in pre-B ALL and T-ALL. We conclude that quantitative flow cytometry of TdT re-establishes the diagnostic value of this enzyme and has potential applications for the study of minimal residual disease.

Acute Disease↗
PubMed1995

[Phenotypical diagnosis of Japanese chronic lymphocytic leukemia--an international cooperative study based on the French-American-British classification of mature B-cell leukemias].

To better understand the accuracy in the diagnosis of chronic lymphocytic leukemia (CLL) and characterize the clinical features of CLL in Japan, where the disease is extremely rare, an international cooperative study was conducted by hematologists between Japan and UK. Blood and bone marrow films from 36 patients with a possible-diagnosis of CLL were referred to two laboratories of Nagasaki University Hospital (Nagasaki) and Royal Marsden Hospital (London). According to the FAB criteria, typical CLL 16 and CLL/PL 2, a subtype of atypical CLL, were completely accordant in diagnosis. However, phenotypical diagnosis of CLL mixed, the other of atypical CLL, and intermediate lymphocytic leukemia (ILL) in leukemic phase often gave inconsistent results. Especially, 8 cases of atypical CLL designated as likely CLL were equivocal between CLL and ILL, suggesting clinical feature more close to typical CLL than ILL. This indicates the presence of a relatively high incidence of atypical CLL in Japan which dose not exactly fit with the FAB Criteria. Finally, we would like to emphasize that an international cooperative study allows improvement of accuracy in diagnosis and better understanding of the disease entity of lymphoid malignancies, having on ethnically different morbidity.

Aged↗