T-chronic Lymphocytic Leukemia Research Articles

ANTI-CD52 TREATMENT EXPERIENCE IN A T-CELL PROLYMPHOCYTIC LEUKEMIA PATIENT:CASE REPORT

T-cell prolymphocytic leukemia (T-PLL) is a rare and highly aggressive T cell neoplasm with rapidly progressing clinical course. T-PLL accounts for 2% of mature lymphocytic leukemia in adults. Median overall survival with modern therapy is reported one to three years. Here we report a T-PLL patient with peritoneum involvement and progressive ascite despite anti-CD52 treatment. A 65-year-old man with diabetes mellitus was admitted to hospital due to fatigue for a few weeks. Laboratory workup revealed that white blood cell count 469 × 103/µl (90% lymphocytes), haemoglobin of 11.4 g/dl, platelets of 104 × 103/µl. Medium sized atypical lymphoid cells with partial chromatin condensation and a visible nucleolus were observed on blood smear. On physical examination, palpable inguinal lymph nodes, splenomegaly 3 cm below the rib margin and a palpable lesion on the helix of left ear were noticed. Punch biyopsy of skin lesion was reported as a mature and immature T cell infiltration which are CD3 and CD10 positive and Tdt, CD34, CD20, CD99 negative. Flow cytometric study of peripheral blood sample was revealed that T-Chronic Lymphocytic Leukemia (T-CLL). FMC protocol (fludarabine, mitoxantrone, and cyclophosphamide ) was initiated and followed by intravenous alemtuzumab at a dose of 3 mg on day 1, 10 mg on day 2 and 30 mg on day 3. However after two months of anti-CD52 treatment, his general situation dete­riorated and pleural effusion and abdominal distension developed due to massive ascites. Small, mature lymphocytic cell infiltration was shown in ascites fluid on cytological examination. He died after six months of diagnosis. T-PLL is a very aggressive disease with a median survival of less than 1 year. Not all patients diagnosed with T-PLL require treatment immediately.Currently, IV alemtuzumab (anti-CD52) is the accepted best avaliable treatment with very high response rates when given as first-line treatment. However, treatment is notcurative and a minority of T-PLL patients experience long-term disease-free survival.

Clinical and laboratory features of T-cell prolymphocytic leukemia in China

To investigate the clinical and laboratory characteristics and survival of Chinese patients with T- cell prolymphocytic leukemia (T-PLL). Eleven patients with T-PLL admitted in our hospital from Jan 2006 to Oct 2012 were retrospectively analyzed. Of the 11 patients, nine were males and two females, with the median age of 56.0(19-69) years old. All the patients, except for three, presented with leukocytosis. The incidence of hyperleukocytosis (1/11) was less frequent than that in the British series (75%) (P=0.000). Lymphocyte counts in peripheral blood were increased in 9 of the 11 patients with the median absolute lymphocyte count (ALC) of 17.22(0.58-148.83)×10⁹/L. Superficial lymphadenopathy and splenomegaly were the most common physical signs. It was common that serum lactate dehydrogenase (LDH) and beta 2 microglobulin(β2-MG)were higher than normal level. All cases were positive for CD2/CD3/CD5/TCRαβ, negative for CD1a /HLA-DR and TdT, and most of them were strong positive for CD7 expression. By chromosome analyses, most cases. (9/10) have normal chromosome. This rate is significantly higher than that of the British and American series (3% and 25%, respectively) (P=0.000, P=0.001). The 14q11 abnormality and trisomy 8q, which are common among Western cases, were not observed in any of our cases. With a median follow-up of 23.0 months, three patients died. Two year progress free survival (PFS) and overall survival (OS) were 53.3% and 50%, respectively. There were 3 patients with PFS over a number of years, whether it should be considered as the T-chronic lymphocytic leukemia (T-CLL) is worthy of further studies. The common clinical manifestations of T-PLL patients were increased lymphocyte counts and lymphadenopathy as well as splenomegaly. And most cases have high level of blood LDH and β2- MG and normal chromosome karyotype.

Inversion 14q in acute lymphoblastic leukemia of B-lineage

Many types of leukemia are associated with specific chromosomal rearrangements. Inversion 14(q11q32) has been reported to be specifically associated with post-thymic T-cell malignancies, including T-chronic lymphocytic leukemia, T-prolymphocytic leukemia, and adult T-cell leukemia/lymphoma. We have previously reported its occurrence in T-cell acute lymphoblastic leukemia. Recently, we encountered a case of acute lymphoblastic leukemia with inv(14)(q11q32), which surprisingly showed a B-cell immunophenotype (CD10+CD19+HLA-DR+Igμ−).

Trisomy 8q due to i(8q) or der(8) t(8;8) is a frequent lesion in T‐prolymphocytic leukaemia: four new cases and a review of the literature

Cytogenetic abnormalities found in four cases of T-cell prolymphocytic leukaemia (T-PLL) are described. An isochromosome 8q was found in three patients and a t(8;8) in one. In the four cases, karyotypes were complex and showed a high degree of instability. In addition, we reviewed 27 published cases of cytogenetically studied T-PLL. On the whole, the most frequently recurring anomalies in T-PLL are 14q lesions with nonrandom breakpoints, inversion (14)(q11q32) or tandem translocations (14;14) (not seen in any of our cases) and trisomy for 8q. mainly due to i(8q), found in more than 40% of patients each. Similar structural anomalies were found almost as frequently among the 23 cytogenetically studied cases of so-called T-chronic lymphocytic leukaemia (T-CLL) reported prior to 1989. It is now accepted that the T-cell counterpart of B-CLL either does not exist or is exceedingly rare and thus previously reported cases of T-CLL sharing the chromosomal characteristics of T-PLL may well have been misdiagnosed examples of T-PLL. Isochromosomes 8q are exceptionally found in other types of haematological malignancies. However, i(8q) could not be shown to be the primary lesion in any case in T-PLL and the role of trisomy for 8q, as well of the associated monosomy 8p, is entirely unknown.

An HTLV‐I carrier who developed CD4 + T‐CLL expressed the IL‐2 receptor β chain alone without expressing the α chain

We describe a case of T-chronic lymphocytic leukaemia (T-CLL) with monoclonal proliferation of CD3+4+8- T cell expressing the interleukin 2 receptor (IL-2R) beta chain without expressing the alpha chain. Southern blot analysis of T-cell receptor beta chain gene revealed rearranged bands. The serum antibody was positive against human T-cell lymphotropic virus type I (HTLV-1)-associated antigens, but monoclonal integration of proviral DNA was not detected in the leukaemic cells. In accordance with the expression of IL-2R beta chain, the leukaemic cells proliferated in response to exogenous IL-2 without prior stimulation. However, culture supernatants of these cells did not show IL-2 activity. Since the role of the IL-2R beta chain in freshly isolated cells from T-CLL patients is not well understood, detailed analysis of this case would give us valuable information on the role of IL-2/IL-2R system in the proliferation of the leukaemic T cells.

T-Cell Malignancies With Mature Phenotypes: Altered Cell Cycle Regulation by HLA Class I Molecules

Soluble anti-HLA class I monoclonal antibodies (MoAbs) modulate normal T-lymphocyte proliferation induced via the CD3/Ti and the CD2 pathway, but do not induce proliferation of normal T lymphocytes in the absence of additional mitogenic stimuli. In this report, we show that anti-HLA class I MoAbs induce DNA synthesis in peripheral blood mononuclear cells from a patient with a CD4+CD8+T-prolymphocytic leukemia (T-PLL) and from a patient with a CD4-CD8+ T-chronic lymphocytic leukemia (T-CLL), in the absence of detectable additional mitogenic stimuli. Proliferation of leukemic T cells is induced by both whole Igs and Fab' fragments of anti-HLA class I MoAbs, arguing in favor of their direct interactions with the proliferating cells as the mechanism underlying the mitogenic effect. This interpretation is also supported by the ability of anti-HLA class I MoAbs to induce proliferation of leukemic T-cell preparations, depleted of accessory cells. DNA synthesis in T-CLL and T-PLL cells is preceded by expression of G1-specific messenger RNAs, ie. c-myc, 2F1, Tac, and interferon-gamma, in activated cells. Cell proliferation is inhibited by the protein kinase C inhibitor H7, indicating that activation of this enzyme is required for the mitogenic effect of anti-HLA class I MoAbs. The latter inhibit the proliferation of T-CLL cells as well as that of normal T cells stimulated with anti-CD3 MoAbs and enhance that of both types of cells stimulated with anti-CD2 MoAbs. In addition, anti-HLA class I MoAb Q6/64 in combination with anti-CD2 MoAb 9.6 or MoAb 9-1 induces proliferation of leukemic T cells to a greater extent than the individual MoAbs, but is not mitogenic for normal T cells. Anti-HLA class I MoAbs restore the cytolytic activity of T-CLL cells that is lost after 5 days of incubation of control medium, suggesting that HLA class I antigens may mediate a signal contributing to the activation state. The present results indicate that leukemic T-cell proliferation can be triggered via HLA class I molecules and suggest a potential role for these antigens in the in vivo growth of malignant clones.

T-cell malignancies with mature phenotypes: altered cell cycle regulation by HLA class I molecules

Soluble anti-HLA class I monoclonal antibodies (MoAbs) modulate normal T-lymphocyte proliferation induced via the CD3/Ti and the CD2 pathway, but do not induce proliferation of normal T lymphocytes in the absence of additional mitogenic stimuli. In this report, we show that anti-HLA class I MoAbs induce DNA synthesis in peripheral blood mononuclear cells from a patient with a CD4+CD8+T-prolymphocytic leukemia (T-PLL) and from a patient with a CD4-CD8+ T-chronic lymphocytic leukemia (T- CLL), in the absence of detectable additional mitogenic stimuli. Proliferation of leukemic T cells is induced by both whole Igs and Fab' fragments of anti-HLA class I MoAbs, arguing in favor of their direct interactions with the proliferating cells as the mechanism underlying the mitogenic effect. This interpretation is also supported by the ability of anti-HLA class I MoAbs to induce proliferation of leukemic T- cell preparations, depleted of accessory cells. DNA synthesis in T-CLL and T-PLL cells is preceded by expression of G1-specific messenger RNAs, ie. c-myc, 2F1, Tac, and interferon-gamma, in activated cells. Cell proliferation is inhibited by the protein kinase C inhibitor H7, indicating that activation of this enzyme is required for the mitogenic effect of anti-HLA class I MoAbs. The latter inhibit the proliferation of T-CLL cells as well as that of normal T cells stimulated with anti- CD3 MoAbs and enhance that of both types of cells stimulated with anti- CD2 MoAbs. In addition, anti-HLA class I MoAb Q6/64 in combination with anti-CD2 MoAb 9.6 or MoAb 9–1 induces proliferation of leukemic T cells to a greater extent than the individual MoAbs, but is not mitogenic for normal T cells. Anti-HLA class I MoAbs restore the cytolytic activity of T-CLL cells that is lost after 5 days of incubation of control medium, suggesting that HLA class I antigens may mediate a signal contributing to the activation state. The present results indicate that leukemic T-cell proliferation can be triggered via HLA class I molecules and suggest a potential role for these antigens in the in vivo growth of malignant clones.

Immunogenetic analysis of bone marrow aspirates in patients with non‐hodgkin lymphomas

The immunogenetic analysis (IGA) on the staging bone marrow aspirates in 15 patients with non-Hodgkin lymphoma (NHL) is reported. We found the sensitivity of IGA and morphologic examination in detecting bone marrow involvement by malignant lymphoma to be 91% and 82%, respectively. In 11 cases there was agreement between the morphologic findings and IGA. In 8 of these 11 cases, IGA confirmed the morphologic involvement of the bone marrow by demonstrating clonal rearrangement of either the immunoglobulin heavy- and/or light-chain or the T-cell receptor beta chain (TCR) genes. In 3 of these 11 cases, morphology showed no involvement and IGA showed germline configurations for both the immunoglobulin heavy- and light-chain or the TCR genes. In 2 additional cases the techniques proved to be complementary, as involvement was detected by only 1 of the 2 procedures. In 1 of these 2 cases, IGA showed gene rearrangement while morphologic examination was negative for involvement by NHL, while in the other case, morphologic examination showed involvement by NHL, but IGA did not show gene rearrangement. IGA was also useful in determining the clonality of solitary lymphoid nodules in the 2 remaining cases when morphologic interpretation was equivocal. In the 12 cases with bone marrow involvement, the immunophenotype and immunogenotype agreed in 11 cases. In the one case in which there was a discordance between the immunophenotype and immunogenotype, the immunophenotype was incorrectly interpreted as B-cell lineage, while the immunogenotype demonstrated a T-cell lineage. IGA also demonstrated a clonal population in 1 case of T-chronic lymphocytic leukemia where other techniques could not demonstrate the clonality of the pathologic process. IGA analysis may detect bone marrow involvement in NHL which may not be detected by morphologic examination because of patchy distribution.

Rearrangement of the T-cell receptor delta genes in human T-cell leukemias

Two distinct types of T-cell receptors (TCR), designated alpha beta and gamma delta, have been identified on the surface of T cells. In the adult, T cells bearing the gamma delta TCR are a minority and they have the phenotype CD3+, CD4-, CD8-/+. By using appropriate probes, rearrangements of the TCR alpha, beta, and gamma genes have been extensively investigated in a variety of lymphoproliferative disorders. Because the TCR delta gene has been cloned only recently, no comparable information exists with respect to this in human leukemias. We report the analysis of the TCR delta gene configuration in 21 T-cell acute and chronic leukemias, 40 B-cell leukemias, 4 acute myeloid leukemias of difficult classification, and 12 normal controls. The TCR delta genes were structurally modified in all T-cell disorders and in germ-line configuration in all controls and all but one case of non-T-cell leukemias tested. In one case of T-chronic lymphocytic leukemia (CD3+, CD4-, CD8+) we found rearrangement and expression of TCR gamma and delta (but not alpha and beta), suggesting that leukemic transformation took place in a cell bearing a TCR gamma delta rather than a TCR alpha beta. In two cases of pre-T-acute lymphoblastic leukemia, only delta was rearranged out of the three TCR genes tested. This finding is in keeping with the suggestion that the TCR delta gene might be the first to rearrange in T cell ontogeny, and that its mode of rearrangement may play a role in the subsequent choice of the cell between production of a TCR alpha beta or gamma delta. Thus, TCR delta chain gene analysis can provide novel information of the clonal nature of T-cell disorders, particularly if the analysis of the beta and gamma genes has not been helpful.

Rearrangement of the T-Cell Receptor δ Genes in Human T-Cell Leukemias

Two distinct types of T-cell receptors (TCR), designated alpha beta and gamma delta, have been identified on the surface of T cells. In the adult, T cells bearing the gamma delta TCR are a minority and they have the phenotype CD3+, CD4-, CD8-/+. By using appropriate probes, rearrangements of the TCR alpha, beta, and gamma genes have been extensively investigated in a variety of lymphoproliferative disorders. Because the TCR delta gene has been cloned only recently, no comparable information exists with respect to this in human leukemias. We report the analysis of the TCR delta gene configuration in 21 T-cell acute and chronic leukemias, 40 B-cell leukemias, 4 acute myeloid leukemias of difficult classification, and 12 normal controls. The TCR delta genes were structurally modified in all T-cell disorders and in germ-line configuration in all controls and all but one case of non-T-cell leukemias tested. In one case of T-chronic lymphocytic leukemia (CD3+, CD4-, CD8+) we found rearrangement and expression of TCR gamma and delta (but not alpha and beta), suggesting that leukemic transformation took place in a cell bearing a TCR gamma delta rather than a TCR alpha beta. In two cases of pre-T-acute lymphoblastic leukemia, only delta was rearranged out of the three TCR genes tested. This finding is in keeping with the suggestion that the TCR delta gene might be the first to rearrange in T cell ontogeny, and that its mode of rearrangement may play a role in the subsequent choice of the cell between production of a TCR alpha beta or gamma delta. Thus, TCR delta chain gene analysis can provide novel information of the clonal nature of T-cell disorders, particularly if the analysis of the beta and gamma genes has not been helpful.

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.

RAB-1: A new monoclonal antibody to leukemic hairy cells

RAB-1, a new monoclonal antibody (McAb) to human leukemic hairy cell (HC) was produced. Using indirect immunofluorescence methods and microscopic or flow cytometric analysis, it was found that the RAB-1 antigen was expressed on few resting B cells and not on resting T lymphocytes, platelets, monocytes, erythroid and myeloid cells. RAB-1 expression on malignant cells was as follows: strongly positive in 15/15 hairy cell leukemia (HCL), negative with non-T and T-acute lymphoblastic leukemia and T-chronic lymphocytic leukemia (CLL); weakly expressed on myeloma and Waldenstrom cells; moderately on 10–25% of the cells in 4/10 B-CLL and 6/10 B lymphomas and in 7/7 B-prolymphocytic leukemia (PLL). Amongst human cell lines that were tested, RAB-1 reacted strongly with one HC line, moderately with the EBV-lymphoblastoid Daudi and Raji Burkitt's lines and was not expressed on Ramos, ALL, myeloid and erythroid cell lines. Normal B cells activated with PWM or anti-μ beads, and malignant B cells activated with anti-μ and TPA did not show an increase of expression of RAB-1 antigen. Interestingly, 30–40% of T4-Class II antigen positive cloned cells and T cells activated with PHA and Con.A expressed RAB-1, suggesting that this McAb recognizes surface molecule, newly induced during T-cell activation and constitutively expressed on HC and some B-cell malignancies.

Dipeptidylaminopeptidase IV activity in normal and leukemic T-cell subpopulations.

Dipeptidylaminopeptidase IV (DAP IV) cytochemical reactivity was investigated in monoclonal antibody defined T-lymphocyte subpopulations from normal blood and in cells from a series of T-cell leukemias of defined immunologic phenotype. A combined monoclonal antibody/immunocolloidal gold technic, which enabled simultaneous visualisation of immunogold label and DAP IV reactivity, was used to study enzyme reactivity in normal T-cell subpopulations. Single or several discrete granules of DAP IV reaction product were observed in 72% of OKT3+ and OKT4+ cells, whereas a significantly (P less than 0.01) lower percentage of OKT8+ cells (41%) displayed positivity; B-cells were invariably DAP IV negative. In the T-cell leukemias, DAP IV reactivity was strongest in T-lymphoblastic lymphoma and T-prolymphocytic leukemia cells. In contrast, DAP IV activity was absent or expressed in a minority of cells of the more immature T-acute lymphoblastic leukemia. The enzyme reaction also was negative in lymphocytes from other mature T-cell leukemias: T-chronic lymphocytic leukemia (OKT8+), adult T-cell lymphoma-leukemia, and Sezary syndrome (both OKT4+). DAP IV expression did not parallel that of acid phosphatase or alpha-naphthyl acetate esterase in leukemic T-lymphoid cells except in T-lymphoblastic lymphoma and T-prolymphocytic leukemia, where a strong reaction with the three hydrolytic enzymes was observed.

Ultrastructural cytochemistry of chronic T-cell leukaemias. A study with four acid hydrolases.

The ultrastructural localization of four acid hydrolases (acid phosphatase, beta-glucuronidase, beta-glucosaminidase and alpha-naphthylacetate esterase) has been studied in lymphocytes from 16 patients with three types of chronic T-cell leukaemia, namely, T-prolymphocytic leukaemia (T-PLL), T-chronic lymphocytic leukaemia (T-CLL) and adult T-cell lymphoma leukaemia (ATLL). Different patterns of enzyme distribution were observed in the leukaemic T-cells from these disorders. In T-PLL, reactivity for the four acid hydrolases was confined to single or a few large granules. Gall bodies were reactive for beta-glucuronidase, b-glucosaminidase and alpha-naphthylacetate esterase but apparently unreactive for acid phosphatase. In T-CLL, scattered small- to medium-size cytoplasmic granules and many parallel tubular arrays were strongly reactive for acid phosphatase, beta-glucuronidase and beta-glucosidase but showed no reactivity for alpha-naphthylacetate esterase. Intermediate features were observed in ATLL. The observed differences in enzyme reactivity reflect a different content of lysosomal granules in the various types of leukaemic T-cells. They also suggest that similar differences may be found in normal T-lymphocyte subsets.

Dipeptidylaminopeptidase IV (DAP IV) activity in normal and malignant T-cell subsets as defined by monoclonal antibodies.

The activity of dipeptidylaminopeptidase IV (DAP IV) was investigated by a cytochemical method in isolated fractions of normal peripheral blood mononuclear cells and malignant cells from 9 patients with chronic T-cell leukaemia. A positive DAP IV reaction was observed in 52% of normal T cells, a consistent negative reaction in normal B cells and monocytes. 2 distinct T-cell subsets, helper/inducer cells (T4+/T8-) and cytotoxic/suppressor cells (T4-/T8+), were negatively selected by complement-mediated cytolysis utilizing the monoclonal antibodies OKT4 and OKT8. On examination of these T-cell subsets a positive DAP IV reaction was restricted to the majority of normal T4+/T8- cells. The malignant cells from 3 patients with T-chronic lymphocytic leukaemia, expressing the cytotoxic/suppressor phenotype (T4-/T8+) lacked DAP IV activities. In contrast, almost all leukaemic cells from 3 other cases, expressing the helper/inducer phenotype (T4+/T8-), were strongly positive. Despite their T4+/T8- phenotype, the malignant cells from 3 patients with Sézary syndrome were completely DAP IV negative. These findings suggest that the DAP IV reaction may be helpful in the further characterization of normal and malignant T-cell subsets.

Morphological and cytochemical features of adult T-cell lymphoma-leukaemia.

T-cell malignancies may be recognised in several distinctive forms: T-lymphoblastic leukaemia and lymphoblastic lymphoma which are proliferations of immature T cells, and a heterogeneous group of proliferative disorders with a mature T-cell phenotype, T-chronic lymphocytic leukaemia, T-prolymphocytic leukaemia and the cutaneous T-cell lymphomas [1]. Within this spectrum of diseases, a distinctive T-cell leukaemia-lymphoma affecting black adults of West Indian/Caribbean origin has been recognised by our group [2] and designated adult T-cell leukaemialymphoma (ATLL). The salient features of the disease include its occurrence in black West Indians, the presence of high titres of antibody against the p 24 structural core protein of human T-cell leukaemia-lymphoma virus (HTLV), severe hypercalcaemia without bone lesions, lymphadenopathy, high WBC and short survival. Immunologically the malignant cells are of mature post-thymic phenotype (E +, TdT−, OKT3+, OKT6−), and in those cases tested with OKT4 and OKT8 monoclonal antibodies, of helper/inducer phenotype (OKT4+, OKT8−).KeywordsAtypical Lymphoid CellCytochemical FeatureAcid Phosphatase ReactionElectron Microscopic MorphologyStructural Core ProteinThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Antigenic characterization of a T-CLL with heteroantisera and monoclonal antibodies: evidence for the T cell lineage of an Ia-positive, Fc-IgG--positive, suppressor-cell subpopulation.

In a previous report, peripheral blood mononuclear T cells from a patient with T-chronic lymphocytic leukemia (T-CLL) were shown to bear receptors for the Fc portion of IgG (T gamma). Moreover, the ability of these cells to rosette with sheep erythrocytes was strongly inhibited by a preincubation of the cells with theophylline. These data indicated that they represent a highly purified subpopulation of Fc-IgG receptor-positive, low-affinity rosetting cells with in vitro suppressor activity on lectin-induced proliferation of normal lymphocytes. They also were reactive in antibody-dependent cell-mediated cytotoxicity but had no reactivity in natural killer cell assays. These cells were studied in this report with several heteroantisera and monoclonal antibodies. Results indicate that these T-CLL cells express a T cell antigenic pattern (OKT-3+) and the majority are Ia positive. They also react with the OKT-8 reagent (a reagent detecting the subset of T cells that contains the cytotoxic/suppressor cells), whereas they are negative with OKT-4 (which reacts with the subset of T cells that contains helper cells) and OKT-6 (thymocyte) antibodies. Heteroantisera also support the results obtained with monoclonal reagents. Despite some recent evidence showing that a high percentage of T gamma cells may belong to the monocyte-myeloid lineage, these T-CLL cells were negative with OKM-1, a monoclonal antibody reported to detect a monomyeloid antigen. These results suggest that a distinct subpopulation of suppressor T cells can be identified by membrane-marker phenotyping.

Surface Antigens on Malignant Sézary and T-CLL Cells Correspond to Those of Mature T Cells

Abstract Tumor cells from eight adult patients with T-cell chronic malignancies were investigated with a series of monoclonal antibodies recognizing T- cell differentiation antigens. This series allowed definition of discrete subpopulations of mature T cells with functional specialization. All six patients with Sezary syndrome and one patient with T-chronic lymphocytic leukemia had cells with the same phenotype as normal helper/inducer T cells, whereas the other patient with T- chronic lymphocytic leukemia had cell with the same phenotype as normal cytotoxic/suppressor T cells. Some clinical manifestations observed in these patients may reflect retention of functional activities by their malignant cells.

Surface antigens on malignant Sezary and T-CLL cells correspond to those of mature T cells

Tumor cells from eight adult patients with T-cell chronic malignancies were investigated with a series of monoclonal antibodies recognizing T-cell differentiation antigens. This series allowed definition of discrete subpopulations of mature T cells with functional specialization. All six patients with Sézary syndrome and one patient with T-chronic lymphocytic leukemia had cells with the same phenotype as normal helper/inducer T cells, whereas the other patient with T-chronic lymphocytic leukemia had cell with the same phenotype as normal cytotoxic/suppressor T cells. Some clinical manifestations observed in these patients may reflect retention of functional activities by their malignant cells.

Cell membrane enzymes: L-gamma-glutamyl transpeptidase, leucine aminopeptidase, maltase and trehalase in normal and leukaemic lymphocytes.

Several cell-membrane enzymes, which serve functions in amino acid and sugar transport, were measured in peripheral blood lymphocytes from chronic B and T lymphocytic disorders, blast cells in acute leukaemias, and in normal lymphocytes from cord blood, peripheral blood of adults, tonsils and bone-marrow plasma cells in myelomatosis. The specific activities of L-gamma-glutamyl transpeptidase, maltase and trehalase were low, as compared with those measured in normal blood lymphocytes, in the acute leukaemias and in the chronic B-cell disorders. In myelomatosis and in the chronic T-cell disorders, the specific activity of these three enzymes was in the normal range or above normal. The specific activity of leucine aminopeptidase was low in all the chronic B-cell disorders and in some of the lymphoblastic leukaemias. It was elevated in Sézary syndrome cells but low in T-chronic lymphocytic leukaemia. All four enzymes were lower than normal in cord blood lymphocytes and higher than normal in tonsils. These findings are discussed in relation to the patterns of lymphoid cell differentiation and maturation in normal tissues and in leukaemic states.