Lymphoblastic leukaemia in Siamese twins: evidence for identity.
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DNA, Neoplasm↗
Biomedical subjects
E Matutes
Publications and source records attributed to E Matutes.
Studies in healthy human T-cell-leukemia lymphoma virus (HTLV-I) carriers from the Caribbean.
Six healthy relatives of 3 adult T-cell leukemia lymphoma (ATLL) patients and 6 members of a Caribbean family immigrant to the UK have been investigated for the presence of HTLV-I and expression of interleukin 2 (IL-2) receptors. Serum antibodies to HTLV-I were detected in all but 4 samples. Four to 10% of circulating cells from 3/4 seropositive donors studied displayed IL-2 receptors (anti-Tac+) and were shown to be convoluted lymphocytes by light microscopy morphology and immunoelectronmicroscopy. After 5 to 28 days in culture, cells from 4 seropositive donors reacted with monoclonal antibodies (MAbs) against the HTLV-I core proteins, p19 and p24, and released retrovirus particles. Similar experiments with blood from 3 seronegative donors from the same families and 4 normal controls proved negative. Our findings indicate that seropositive individuals harbour the virus in a population of T-lymphocytes which may then acquire receptors for IL-2. These individuals are at risk of developing ATLL.
Antibodies, Viral↗
Correlation between chromosomal abnormalities and blast phenotype in the blast crisis of Ph-positive CGL.
We carried out cytogenetic analysis in 23 patients with Ph-positive chronic granulocytic leukemia in blast crisis. In all cases the type of blast cell was characterized by cytochemistry, immunologic markers, and ultrastructural studies. Twelve cases were classified as myeloid transformation, six as lymphoid, two as mixed (lymphoid and myeloid), and two were unclassifiable. Duplication of Ph was the most frequent abnormality in the whole series. Trisomy 8, i(17q) and trisomy 19 were seen only in patients with myeloid blast crisis (53%, 30%, and 23%, respectively). Our findings suggest that the nature of additional chromosome abnormalities arising in blasts with features of myeloid differentiation are different from those in blasts showing lymphoid differentiation.
Adult↗
The nature of T-chronic lymphocytic leukaemia.
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Humans↗
Purification of haemopoietic progenitor cells from patients with chronic granulocytic leukaemia using percoll density gradients and elutriation.
Purification of haemopoietic progenitor cells from chronic granulocytic leukaemia buffy coat preparations requires a multistep approach using complementary cell separation techniques. In this study Percoll density gradient centrifugation and centrifugal elutriation were used to isolate large numbers of immature progenitor cells. Percoll density gradients were valuable as a first separation step: CFU-GM and CFU-GEMM could be enriched 75-fold in a light density fraction of d less than 1.056 g/ml and the technique could be adapted to cope with more than 10(10) buffy coat leucocytes. Progenitors cells were concentrated 3-fold by elutriation used as single method to separate buffy coat cells or when used to purify further light density Percoll fractions. When Percoll gradients and elutriation were used sequentially, undifferentiated mononuclear cells were enriched to more than 90% purity and between 5% and 40% of these cells formed CFU-GM or BFU-E colonies consisting of more than 40 cells. The enriched fractions were further characterized with monoclonal antibodies. The density and elutriation profiles of these colony forming cells resembled corresponding profiles of cells that reacted with the monoclonal antibody BI-3C5, which recognizes an antigen on primitive haemopoietic progenitor cells. Physical separation methods are a valuable first stage in the attempt to procure relatively pure myeloid progenitor cell populations, whose characteristics can then be further studied at a cellular or molecular level.
Cell Separation↗
The morphological spectrum of T-prolymphocytic leukaemia.
The morphology of the cells from 29 cases of T-prolymphocytic leukaemia (T-PLL) was studied by light (LM) and transmission electron microscopy (TEM) and was compared with that of 33 B-cell PLL. The membrane phenotype of T-PLL cells was T4+, T8- in two-thirds of the cases, others being T4- T8+ or T4+ T8+. Two morphological types of T-PLL were defined according to the nuclear features: regular (55% of cases) and irregular (45% of cases). T-PLL cells with a regular, round or oval, nuclear outline resembled B-PLL cells but had less abundant cytoplasm and a higher nucleo-cytoplasmic ratio. Irregular T-prolymphocytes displayed a distinct convoluted nucleus. A 'small-cell' variant of T-PLL was recognized by TEM in six cases in which the diagnosis was uncertain by LM. A characteristic of all types of T-prolymphocytes by LM was the presence of a deep basophilic cytoplasm which by TEM corresponded to clusters of ribosomes and endoplasmic reticulum. No differences in clinico-haematological features or membrane markers were apparent between the morphological types of T-PLL, although it was noted that the three T4- T8+ cases had irregular cells and four of the small cell variant were T3- T4+. TEM permits a more precise assessment of the cytoplasmic organelles and nucleolus than LM analysis and facilitates the distinction between T-PLL and other leukaemias with a mature T-cell phenotype, namely adult T-cell leukaemia/lymphoma. Sezary syndrome and T-chronic lymphocytic leukaemia.
Aged↗
Megakaryoblastic transformation of myelofibrosis with expression of the c-sis oncogene.
We describe a case of primary myelofibrosis which terminated in an acute megakaryoblastic leukaemia with massive marrow fibrosis and osteosclerosis. The megakaryocyte lineage of the terminal phase was confirmed by ultrastructural and surface marker studies of the blast cells. The leukaemic phase was associated with the presence of large numbers of progressively more immature megakaryocyte progenitors in the peripheral blood. The expression of c-sis mRNA in these blast cells was significantly higher than in normal mononuclear cells. Activation of the c-sis protooncogene leading to increased production of platelet-derived growth factor could be related to the progressive fibrosis observed.
Adult↗
Coexpression of T- and B-markers in a lymphoproliferative disorder.
An atypical case of lymphoproliferative disorder in which T- and B-cell antigens were coexpressed in the neoplastic cells is described. The disease was characterised by hepatosplenomegaly, lymphadenopathy, a low WBC (5 X 10(9)/l) and bone marrow infiltration. The predominant cell population (greater than 70%) comprised lymphoid cells with a range of nuclear irregularities and included some blast cells. 90% of the peripheral blood lymphocytes showed a mature T-helper phenotype (E+, T11+, T3+, T4+, T8-, T6-, TdT-) with coexpression of the specific B-markers B1 and FMC7, in 90% and 50% of cells, respectively. HLA-DR antigens were present in 55% of cells while surface and cytoplasmic immunoglobulins (Ig) were detected in less than 10% of cells. Molecular investigations with appropriate probes showed evidence of T-cell receptor gene rearrangement but no rearrangement for the genes of the Ig-heavy and -light chains. Cytogenetic studies revealed a translocation t(10;19) (p12; q13) in all the metaphases analyzed. This case demonstrates that the study of neoplastic cells with a battery of monoclonal antibodies may disclose the existence of a hitherto unrecognised lymphoid cell population with atypical expression of B- and T-cell antigens. On the other hand, the presence of T-cell receptor gene rearrangement indicates that this is a T-cell disorder with the aberrant co-expression of specific B-cell markers.
Aged↗
Abnormalities of chromosome 7q and Tac expression in T cell leukemias.
Clonal chromosome abnormalities were demonstrated in 13 cases of T cell leukemia with a mature membrane phenotype. The cases comprised two adult T cell lymphoma leukemia (ATLL), five Sézary syndrome (SS), three T prolymphocytic leukemia (T-PLL), and three T chronic lymphocytic leukemia (T-CLL). The presence of clonal chromosome abnormalities in the three cases of T-CLL supports the view that although clinically benign, this disorder probably represents a neoplastic process. Cells from six of 11 patients were tested and found to be reactive with monoclonal antibody (McAb) anti-Tac in the absence of mitogens (two ATLL, two SS, and two T-PLL). Only the two ATLL patients were serologically positive for the human T cell leukemia virus I (HTLV-I), and their cells showed a higher anti-Tac reactivity. Chromosome 7 abnormalities were observed in seven cases (two ATLL, three SS, two T-PLL), and a strong correlation was seen between the presence of a 7q abnormality and the expression of the Tac antigen (T cell growth factor receptor). These findings are discussed in relation to the localization of T cell receptor genes on chromosome 7 and possible mechanisms for the activation of the Tac gene.
Antibodies, Monoclonal↗
An unusual variant of T-CLL: evidence for the existence of a hitherto unrecognized T cell subset.
A case of T-cell chronic lymphocytic leukaemia (T-CLL) with an unusual mature membrane phenotype: E+, CD3+, CD4+, CD8-, M1+, Leu-15+, Fc gamma+, is described. The cells were large granular lymphocytes with slight immature features. Functionally these cells lacked helper, suppressor and NK activity but possessed normal levels of K activity. These findings demonstrate several features not previously described in T-CLL: the coexpression of the antigens detected by T4, M1 and Leu-15 the presence of Fc gamma receptors on CD4+ lymphocytes and the lack of NK activity in M1+, Fc gamma+ cells. This study broadens the known heterogeneity of T-CLL and suggests the existence of a hitherto unrecognized normal T-lymphocyte subset with the same functional and phenotypic characteristics as in the case described here.
Antibodies, Monoclonal↗
T-cell leukaemias with "helper" phenotype in adults.
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Adult↗
Ultrastructural analysis of normal and leukaemic cells by the immunogold method and monoclonal antibodies.
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Acute Disease↗
Reduction in the stearic to oleic acid ratio in leukaemic cells--a possible chemical marker of malignancy.
Total lipid extracts of peripheral blood cells from patients with chronic leukaemias were analysed for relative values of saturation of the eighteen carbon chain length fatty acids (C 18 FA). The results are expressed as saturation index (C 18 S:C 18 U) of the saturated C 18 FA (stearic acid) over the unsaturated C 18 FA (oleic, linoleic and linolenic acids). The saturation indices of the white blood cells (WBC) and the red blood cells (RBC) in specimens from 14 patients with chronic granulocytic leukaemia (CGL) and 17 patients with chronic lymphocytic leukaemias (CLL) were significantly and consistently lower than control specimens. It is proposed that the relative increase in the unsaturated oleic acid could prove to be a chemical marker of malignancy reflecting a deficient cellular control of the process of stearic acid desaturation. The theoretical implications of the implied increase in membrane fluidity for the cells are discussed.
Chromatography, Gas↗
Proliferation in liquid culture of megakaryocytes from the blood of patients with primary myelofibrosis and other myeloproliferative disorders.
Using a short term liquid system we have shown that blood from some patients with primary myelofibrosis (PMF) and chronic granulocytic leukaemia (CGL) in megakaryoblastic transformation (CGL-Mk) gives rise to large numbers of progenitor cells committed to the megakaryocyte (Mk) lineage. As assessed by indirect immunofluorescence the number of cells reacting with three antiplatelet monoclonal antibodies, C17, J15 and AN51, increases during the culture period. There is no equivalent increase in cultures from the blood of normal individuals or patients with essential thrombocythaemia (ET). Furthermore plasma-free supernatants from cultures of the cells from patients with PMF and CGL-Mk stimulate the rate of proliferation of fibroblasts from normal bone marrow. These data provide further evidence for the involvement of the Mk lineage in PMF and CGL and suggest that the excess fibrosis seen in these conditions may be caused by a factor emanating from Mks.
Antibodies, Monoclonal↗
Atypical promyelocytic leukemia (M3) with immature primary granules and t(15;17).
An unusual case of acute myeloid leukemia with a standard t(15;17) is described. While light microscopy morphology was suggestive of acute myeloid leukemia M5a and light microscopy cytochemistry showed 80% of blasts to be strongly positive with Sudan Black B--more consistent with a diagnosis of M4--ultrastructural analysis demonstrated that the predominant cells were promyelocytes with immature primary granules hardly visible with the Romanovsky stains by light microscopy. Because typical cytologic and clinical features of M3 or M3 variant were lacking this atypical case would not have been recognized but for the presence of t(15;17) and the demonstration of promyelocytic features by electron microscopy.
Chromosome Banding↗
Monoclonal antibody OKT17 recognizes most cases of T-cell malignancy.
Membrane phenotype analysis with monoclonal antibodies (McAb) has demonstrated great heterogeneity within the T-cell malignancies. We describe here the reactivity with an anti-T cell McAb, OKT17, in 80 leukaemia samples. Cells from all types of T-cell leukaemia (48 cases), except from the small group of pre-T-ALL, strongly expressed the antigen identified by OKT17 whereas none of the 32 non-T leukaemias were OKT17 positive. When the reactivity of OKT17 was compared with that of other pan-T markers, OKT17 was positive in a larger number of T-cell leukaemias: 87% of cases compared with 74% with E-rosettes and 73% with the McAb 3A1. In the mature or post-thymic proliferations OKT17 was positive in 96% of cases, compared with 77% with E-rosettes and 61% with 3A1. The latter reagent, on the other hand, was better than OKT17 for detecting leukaemias with a thymic phenotype, 100% and 68% of positive cases respectively. The combined use of OKT17, 3A1 and terminal transferase permits a more precise classification of all the T-cell leukaemias according to the main stages of T-cell differentiation.
Antibodies, Monoclonal↗
Characterization of blast cells in chronic granulocytic leukaemia in transformation, acute myelofibrosis and undifferentiated leukaemia. I. Ultrastructural morphology and cytochemistry.
A systematic analysis of the blast cell population was carried out on samples from 50 patients suffering from blast transformation of chronic granulocytic leukaemia (CGL) (31) and of myelofibrosis (4), acute myelofibrosis (AM) (11) and undifferentiated acute leukaemia (4). Transmission electron microscopy (TEM), used in 41 samples, included: morphology and techniques for myeloperoxidase (MPO), platelet-peroxidase (PPO) and acid phosphatase (AP). The majority of cases were also studied by light microscopy cytochemistry and with a battery of cell markers which are reported in the accompanying paper (San Miguel et al, 1985). The characterization of the type(s) of proliferating blasts was made from the integration of ultrastructural and immunological data. TEM morphology allowed the precise recognition of specific granules in basophil and mast-cell precursors and of ferritin particles in blasts of erythroid lineage; these rare cell types were not adequately characterized by other methods. The PPO reaction made possible the identification of pure megakaryoblastic proliferations in 38% of cases, including eight of the 11 with AM; megakaryoblasts were also present in nine of 12 cases with mixed blast cell types. The MPO and AP reactions were useful for the characterization of myeloblasts and monoblasts, respectively. Lymphoblasts could be distinguished from other cell types by TEM morphology and negative MPO and PPO reactions. TEM techniques were valuable for diagnosing correctly the type of blast cell in this study in which only four cases (8%) remained unclassifiable.
Acute Disease↗
Characterization of blast cells in chronic granulocytic leukaemia in transformation, acute myelofibrosis and undifferentiated leukaemia. II. Studies with monoclonal antibodies and terminal transferase.
A panel of 19 monoclonal antibodies (McAb) and the enzyme terminal transferase (TdT) have been applied to the characterization of poorly differentiated blasts from 50 patients with chronic granulocytic leukaemia (CGL) and myelofibrosis in blast crisis (BC), acute myelofibrosis and undifferentiated leukaemia. These cells were also extensively studied by transmission electron microscopy (TEM) (see Polli et al, 1985a). McAb against platelet glycoproteins (GP) showed a high specificity for megakaryoblasts, in particular those reactive with the GPIIb/IIIa complex (J15) and GPIIIa (C15 and C17), which were positive in a higher proportion of blasts than the McAb to GPIb (AN51 and FMC25). Findings with these anti-platelet McAb paralleled those of the platelet-peroxidase (PPO) reaction in 76% of cases studied simultaneously. The PPO reaction was always positive in cases in which two or more of the McAb were reactive with the blast cells. The differences observed suggest, nevertheless, that PPO is more sensitive for megakaryoblasts than the McAb and that this TEM technique should be reserved for cases which are negative with the platelet specific McAb. Of the McAb against myeloid antigens used in this series OKM1 was positive in 50% of cases but the others failed to demonstrate early features of differentiation in myeloblasts and monoblasts. In only three cases were erythroid precursors demonstrated by TEM and these were the only ones reactive with a McAb to glycophorin-A (LICR LON/R10). TdT and the McAb J5 helped in the identification of lymphoblasts which were seen as a 'pure' proliferation in 23% of CGL-BC and as part of blast cell mixtures in another 17% of cases. The McAb reactive to haemopoietic precursor cells (RFB1, FMC8 and OKIa), on the other hand, were of no practical value for the classification of blast cell types. The lineage specificity of several of the McAb used in this study, confirmed by TEM, suggest that these reagents are valuable tools for the characterization of immature blast cells.
Acute Disease↗