Chronic Lymphosarcoma Cell Leukemia Research Articles

Monoclonal Antibody Studies in B(Non-T)-Cell Malignancies

Tumor cells suspensions prepared from 129 B- or non-T cell malignancies were investigated with a panel of 10 monoclonal antibodies and conventional surface marker techniques. Surface immunoglobulin (sIg) and B1 antigen proved to be the most useful markers for B-cell lineage. Six major subtypes of acute lymphoblastic leukemia (ALL) of non-T cell nature are now recognized by these immunological techniques, including null-ALL, Ia-ALL, lymphoid stem cell ALL, pre-pre-B ALL, pre-B ALL and B-ALL. In cases of chronic leukemias and lymphomas of non-T cell nature, 80% of the tumor was defined by sIg and 88% by B1 antigen as definitely of B-cell lineage. The clonal character was also defined in 68% of the tumor on the basis of the detection of predominant single light chain in sIg. Ia-like antigen was detected in almost all cases (96%). Leukemic cells from all cases of chronic lymphocytic leukemia (CLL), chronic lymphosarcoma cell leukemia (CLsCL) and hairy cell leukemia (HCL) reacted with OKIa1 and anti-B1, and leukemic cells from most of them with anti-pan T monoclonal antibody (10.2). In more than half of CLL and CLsCL, leukemic cells were reactive with J5, OKM1, 9.6 and OKT8, but not with OKT3, OKT4 and OKT6. HCL cells had almost the same reactivity with these monoclonal antibodies as CLL and CLsCL cells except that J5 remained unreactive. These results indicated that Japanese CLL, CLsCL and HCL were different from Western ones at least with respect to surface marker characteristics. In cases of lymphomas, heavy chains of sIg were expressed in polyclonal fashion, especially in follicular lymphoma and diffuse lymphomas of medium sized cell type and large cell type, indicating that lymphomas of these types may originate from follicular center cells of the heavy chain switching stage. Anti-T monoclonals were also reactive with lymphoma cells. In about half of follicular lymphomas and diffuse lymphomas of the medium sized cell type, lymphoma cells reacted with 10.2, and less frequently with 9.6, OKT4 and OKT3. On the other hand, only in one or two cases of diffuse lymphoma of the large cell type and of immunoblastic sarcoma (IBS), did tumor cells react with 10.2 and 9.6, but this was exceptional. In more than 25% of IBS, tumor cells also reacted with OKT8, but not with OKT4 and OKT3. These results indicated that anti-T monoclonals are no longer specific for T-cell lineage.(ABSTRACT TRUNCATED AT 400 WORDS)

Isolation and partial characterization of a 72,000-dalton glycoprotein (Tgp72) on human thymus and T cells: possible relationship to mouse Ly-1 antigens.

Abstract A xenoantiserum was raised in guinea pigs to a human T cell antigen (Tgp72) partially purified from cell membrane of T cell leukemia cells from a patient with chronic lymphosarcoma cell leukemia of T cell-type by using sequential chromatographic procedures. The antiserum reacted with all of human thymus and peripheral T cells as well as with a variety of cultured leukemic T cell lines, but not with B cells, granulocytes, and other cultured lymphoid cell lines, including normal B cell, Burkitt, myeloid, and non-T non-B cell lines. Immunoprecipitated material from 125I-labeled thymocyte, T cell, and T cell leukemia cell-surface glycoproteins by this antiserum was analyzed by SDS-polyacrylamide gel electrophoresis, which disclosed a single component with a m.w. of 72K (Tgp72). Further immunochemical data suggest that Tgp72 antigen on human thymus and T cells is an acidic glycoprotein composed of a single polypeptide rather than sulfhydryl-linked subunits, showing a marked electric charge heterogeneity in DEAE anion-exchange resin chromatography. This is further confirmed by the data obtained from 2-dimensional polyacrylamide gel electrophoresis, indicating that Tgp72 is a 72K m.w. glycoprotein with an isoelectric point ranging from 4 to 7. Because of its similarity in tissue distribution and immunochemical characteristics, Tgp72 on human thymus and T cells was assumed to be a human homologue of Ly-1 antigens in murine system.

Distribution of complement receptors on human normal and malignant mononuclear cells

Mononuclear cells from normal human subjects and patients with chronic lymphocytic leukemia (CLL), chronic lymphosarcoma cell leukemia (LCL), and hairy cell leukemia (HCL) were labeled with fluoresceinated, purified human C3b (FI-C3b) and analyzed using the fluorescence- activated cell sorter (FACS). FI-C3b labeled 17.6% +/- 6.0% of peripheral blood mononuclear cells (PBM) from 20 normal subjects, which, when separated by the FACS, consisted of B lymphocytes and approximately 5% monocytes. Analyses in which either monocytes or B lymphcoytes were excluded from consideration demonstrated that both these cell types were labeled by the FI-C3b with a heterogeneous distribution of fluorescence intensity, indicating either heterogeneity of CR density or variable avidity of individual CR for the FI-C3b. FACS profiles of PBM ( < 5% monocytes) from 14 of 15 patients with CLL showed a homogeneous distribution of very low fluorescence intensity, with > 60% of the cells being slightly more fluorescent than unlabeled controls. This low, homogeneous distribution of fluorescence is strikingly similar to profiles of CLL cells labeled with anti-Ig reagents and suggests homogeneity of low CR density and/or avidity. Similarly, CR+ mononuclear cells from five patients with HCL and three patients with LCL displayed more homogeneous FI-C3b labeling than normal CR+ PBM. Homogeneity of FI-C3b binding to CLL, LCL, and HCL cells further supports the concept for a clonal origin for these disorders.

Distribution of Complement Receptors on Human Normal and Malignant Mononuclear Cells

Mononuclear cells from normal human subjects and patients with chronic lymphocytic leukemia (CLL), chronic lymphosarcoma cell leukemia (LCL), and hairy cell leukemia (HCL) were labeled with fluoresceinated, purified human C3b (FI-C3b) and analyzed using the fluorescence-activated cell sorter (FACS). FI-C3b labeled 17.6% +/- 6.0% of peripheral blood mononuclear cells (PBM) from 20 normal subjects, which, when separated by the FACS, consisted of B lymphocytes and approximately 5% monocytes. Analyses in which either monocytes or B lymphcoytes were excluded from consideration demonstrated that both these cell types were labeled by the FI-C3b with a heterogeneous distribution of fluorescence intensity, indicating either heterogeneity of CR density or variable avidity of individual CR for the FI-C3b. FACS profiles of PBM ( < 5% monocytes) from 14 of 15 patients with CLL showed a homogeneous distribution of very low fluorescence intensity, with > 60% of the cells being slightly more fluorescent than unlabeled controls. This low, homogeneous distribution of fluorescence is strikingly similar to profiles of CLL cells labeled with anti-Ig reagents and suggests homogeneity of low CR density and/or avidity. Similarly, CR+ mononuclear cells from five patients with HCL and three patients with LCL displayed more homogeneous FI-C3b labeling than normal CR+ PBM. Homogeneity of FI-C3b binding to CLL, LCL, and HCL cells further supports the concept for a clonal origin for these disorders.

Surface Immunoglobulin Density on Human Peripheral Blood Mononuclear Cells

AbstractThe densities of surface immunoglobulin (sIg) on peripheral blood mononuclear cells (PBM) of normals and patients with chronic lymphocytic leukemia (CLL), chronic lymphosarcoma cell leukemia (LCD, and hairy cell leukemia (HCL) were analyzed using the fluorescence-activated cell sorter (FACS). PBM were labeled with fluorescein conjugates of F(ab')2 fragments of affinity chromatography-purified anti-Fab or class-specific anti-µ, anti-δ, anti-γ, or anti-α. Histograms of relative cell fluorescence, reflecting sIg density, were prepared with the FACS. Anti-Fab-labeled normal PBM demonstrated a homogeneous low-density peak that when separated by the FACS and analyzed cytochemically consisted predominantly of monocytes, whereas brighter-staining cells were predominantly lymphocytes. Anti-µ and anti-δ labeled 9.0% and 8.5% of normal PBM, respectively, the sIg+ cells being virtually all lymphocytes. Cells labeled by anti-γ exhibited low homoge neous sIg density and consisted of more than 80% monocytes. No normal or leukemic PBM were labeled by anti-α. All sIg-positive cells (<5% monocytes) from 12 of 13 patients with CLL had very low homogeneous densities of sIg and bore sIgM, whereas cells from 9 of 13 and 2 of 13 patients bore sIgD and sIgG, respectively. Similarly, PBM from 2 patients with HCL exhibited low and homogeneous densities of sIgM, sIgD, and sIgG, whereas those from a third patient bore only sIgG. By contrast, the density of sIgM and PBM derived from 3 patients with LCL was very high; sIgD and sIgG densities varied from very high to undetectable in these patients. The different homogeneous densities of sIg on peripheral blood lymphocytes from patients with CLL, HCL, and LCL suggest that these diseases represent malignant transformation of different B-lymphocyte subpopulations.

Surface immunoglobulin density on human peripheral blood mononuclear cells

The densities of surface immunoglobulin (slg) on peripheral blood mononuclear cells (PBM) of normals and patients with chronic lymphocytic leukemia (CLL), chronic lymphosarcoma cell leukemia (LCL), and hairy cell leukemia (HCL) were analyzed using the fluorescence- activated cell sorter (FACS). PBM were labeled with fluorescein conjugates of F(ab')2 fragments of affinity chromatography-purified anti-Fab or class-specific anti-mu, anti-delta, anti-gamma, or anti- alpha. Histograms of relative cell fluorescence, rems of relative cell fluorescence, reflecting slg density, were prepared with the FACS. Anti- Fab-labeled normal PBM demonstrated a homogeneous low-density peak that when separated by the FACS and analyzed cytochemically consisted predominantly of monocytes, whereas brighter-staining cells were predominantly lymphocytes. Anti-mu and anti-delta labeled 9.0% and 8.5% of normal PBM, respectively, the slg+ cells being virtually all lymphocytes. Cells labeled by anti-gamma exhibited low homogeneous slg density and consisted of more than 80% monocytes. No normal or leukemic PBM were labeled by anti-alpha. All slg-positive cells (less than 5% monocytes) from 12 of 13 patients with CLL had very low homogeneous densities of slg and bore slgM, Whereas cells from 9 of 13 and 2 of 13 patients bore slgD and slgG, respectively. Similarly, PBM from 2 patients with HCL exhibited low and homogeneous densities of algM, slgD, and slgG, whereas those from a third patient bore only slgG. By contrast, the density of slgM and PBM derived from 3 patients with LCL was very high; slgD and slgG densities varied from very high to undetectable in these patients. The different homogeneous densities of slg on peripheral blood lymphocytes from patients with CLL, HCL, and LCL suggest that these diseases represent malignant transformation of different B-lymphocyte subpopulations.

Lymphosarcoma cell leukemia: the contribution of cell surface study to diagnosis

Cell surface immunoglobulin, complement receptor, and spontaneous rosette formation with sheep erythrocytes were investigated in 43 patients with malignant lymphoma, including 13 with lymphosarcoma cell leukemia, and in 59 patients with chronic lymphocytic leukemia. The quantity of immunoglobulin on the lymphocyte surface was estimated from the intensity of fluorescent staining with fluorescein-conjugated anti-immunoglobulin antisera. At least two, and probably three, B cell species could be recognized by cell surface study. Cells from chronic lymphocytic leukemia and diffuse well-differentiated lymphocytic lymphoma had sparse amounts of surface immunoglobulin, while the cells of diffuse poorly differentiated lymphocytic lymphoma had large quantities of this material. Nodular lymphoma probably represented a third B-cell subtype with intermediate amounts of surface immunoglobulin. The lymphocytes of chronic lymphosarcoma cell leukemia exhibited the intense surface staining, which was characteristic of the underlying poorly differentiated lymphocytic lymphoma (diffuse or nodular), and could be readily distinguished from the faint-staining chronic lymphocytic leukemia cells.

The clinical correlates of IgM M-components: an analysis of thirty-four patients.

Thirty-four patients with an IgM M-component were evaluated for clinical presentation and course, laboratory data, and histologic findings. An attempt was made to ignore the presence of the IgM M-component and to assign each patient to one of the following categories: Waldenstrom's macroglobulinemia, IgM myeloma, Hodgkin's disease, lymphoma, chronic lymphocytic leukemia, chronic lymphosarcoma cell leukemia, and IgM M-components not associated with an identifiable lymphoproliferative disorder ("benign" M-component). Although transitional forms occasionally occurred, most patients could be readily categorized. The patients with lymphoma, Hodgkin's disease, chronic lymphocytic leukemia, and chronic lymphosarcoma cell leukemia did not appear to behave differently from patients with these disorders who did not have serum IgM M-component. Both for descriptive convenience and for clinical management, continued attempts should be made to separate patients with IgM M-components according to their underlying conditions.

Extensive leukemic infiltration of the gastrointestinal tract in chronic lymphosarcoma cell leukemia

Infiltration of the gastrointestinal tract by leukemia cells is frequently found in chronic lymphocytic leukemia and lymphosarcoma. Although other cases may have been reported which resemble this one, they have not been recognized as chronic lymphosarcoma cell leukemia. Radiation treatment of the infiltrates in the gastrointestinal tract resulted in an excellent response, as shown by x-ray studies, and no evidence of recurrence at autopsy. Persistent hepatosplenomegaly, generalized lymph node enlargement and bilateral pleural effusions were eventually resistant to therapy. An opportunistic lung infection due to Pneumocystis carinii was seen as a complication terminally.

Extensive leukemic infiltration of the gastrointestinal tract in chronic lymphosarcoma cell leukemia: Fromke VL, Weber LW: Am J Med 56: 879–882, 1974

Extensive leukemic infiltration of the gastrointestinal tract in chronic lymphosarcoma cell leukemia: Fromke VL, Weber LW: Am J Med 56: 879–882, 1974

Malignant lymphoma diagnosed at splenectomy and idiopathic splenomegaly. A clinicopathologic comparison.

The clinical, laboratory, and histopathologic findings in 15 cases of malignant lymphoma presenting as splenomegaly and diagnosed at splenectomy were compared with 10 cases of idiopathic splenomegaly. The ages of the patients, the duration of splenomegaly, the hematologic parameters, and the weights of the spleen were similar in the two groups of patients. None of the 15 patients with malignant lymphoma initially diagnosed at splenectomy was considered cured: 8 died with disseminated disease within 2 years, 2 have survived for longer than 3 years with progression to chronic lymphosarcoma cell leukemia, and 5 have been followed for less than 12 months. Idiopathic splenomegaly, an apparently benign inflammatory lesion, may simulate lymphoma clinically and be confused with nodular lymphoma pathologically, particularly when associated with lymphocytic infiltrates of the liver and bone marrow and atypical lymphocytes in the peripheral blood. Splenectomy is indicated in patients with persistent splenomegaly without known contributing or related disease, and care must be exercised in the pathologic distinction between splenic lymphoma and idiopathic splenomegaly.

Cell-surface immunoglobulins in chronic lymphocytic leukemia and allied disorders

Immunoglobulin on the surface of peripheral blood lymphocytes from 57 patients with chronic lymphocytic leukemia (CLL) and allied disorders was investigated by fluorescence microscopy and correlated with circulating immunoglobulin. In 38 of 48 patients with CLL, the predominant surface immunoglobulin identified on peripheral blood lymphocytes was M (IgM) of either kappa or lambda light chain type. In five patients, the predominant surface protein was immunoglobulin G (IgG) of either kappa or lambda type. In three others, the lymphocyte surface immunoglobulin could not be definitely identified and in two, no surface immunoglobulin was detected. Circulating immunoglobulin levels, particularly IgM, were depressed in the majority of patients with CLL. In three subjects with IgM-bearing lymphocytes, the serum contained a circulating IgM M component and three of the five subjects with IgG-bearing cells, had a circulating IgG M component. In three patients with CLL, immunoglobulin disappeared from the cell surface with progression of the disorder, although neoplastic cells remained in the circulation. The amount of immunoglobulin on the surface of cells from patients with chronic lymphosarcoma cell leukemia was much greater than that on cells from patients with CLL, and the surface immunoglobulin pattern in hairy cell leukemia also appeared distinctive. Study of immunoglobulin on the surface of lymphocytes has helped to define the cellular origin and monoclonal nature of CLL, the source of circulating M components in this disease, and the relationship of CLL to other lymphoproliferative disorders. Although technically demanding, the study of surface immunoglobulin should prove useful in clinical medicine.

Immunoglobulins on the surface of neoplastic lymphocytes.

Abstract Peripheral lymphocytes from 25 patients with chronic lymphocytic leukemia (CLL) and three with chronic lymphosarcoma-cell leukemia, and lymph-node cells from three of four with lymphocytic lymphoma bore on their cell surface IgM, which was readily demonstrated with fluorescein-conjugated antiserums. The lymphosarcoma cell differed from the cell of CLL in possessing much more surface immunoglobulin. Light-chain analysis of the surface IgM showed that cells bore either kappa or lambda determinants, but not both, indicating the clonal nature of these neoplasms. The serum of four leukemic patients was also found to contain small amounts of IgM M-components. Since the B lymphocyte (bone-marrow-derived) of laboratory animals bears large amounts of surface immunoglobulin and the T lymphocyte (thymus processed) does not, the findings favor the B-cell origin of these leukemic cells. A less likely possibility is that the CLL lymphocyte is a derepressed T cell.

Chronic lymphocytic leukemia versus chronic lymphosarcoma cell leukemia: Analysis of 496 cases

Review of 496 cases of chronic lymphocytic and chronic lymphosarcoma cell leukemia disclosed a number of minor differences in clinical and laboratory manifestations, but with few exceptions they lacked statistical significance. However, highly significant differences were found in survivorship. It is concluded from these data that morphologic distinction between these two types of chronic lymphocytic leukemia is justified on the basis of the significantly shorter course in the lymphoproliferative disorder which we prefer to designate “chronic lymphosarcoma cell leukemia.” Other pertinent differences do not apppear to exist.

Lymphosarcoma cell leukemia

The clinical and hematologic manifestations of twenty-three patients with lymphosarcoma (LSA) cell leukemia are reviewed. Eleven of these patients had the acute or subacute form of the disease; twelve had chronic lymphosarcoma cell leukemia. The morphologic hallmark of lymphosarcoma cell leukemia is an atypical, large lymphocyte with coarsely reticulated nuclear chromatin and a single prominent nucleolus. The maturity of these cells correlates with the chronicity or acuteness of the leukemic process. The degree of bone marrow involvement appears to constitute the chief difference between lymphosarcoma presenting as lymphoma and lymphosarcoma cell leukemia. Superimposed hemolysis, intercurrent infections and hemorrhagic phenomena were frequent complications. Prognosis could be related to cell maturity. Acute lymphosarcoma cell leukemia has a prognosis comparable to that of acute lymphocytic leukemia; chronic lymphosarcoma cell leukemia has a prognosis which appears to be intermediate between that of acute and chronic lymphocytic leukemia. Differences in clinical manifestations, course and response to therapy warrant the separation of acute and chronic lymphosarcoma cell leukemia from acute and chronic lymphocytic leukemia.