scholarly journals Interferon system in primary acute lymphocytic leukemia cells with or without deletions of the alpha-/beta-interferon genes

Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 2076-2083
Author(s):  
D Grander ◽  
M Heyman ◽  
K Brondum-Nielsen ◽  
Y Liu ◽  
E Lundgren ◽  
...  
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Malignant Cells ◽  
Oligoadenylate Synthetase ◽  
Gene Deletions ◽  
Functional Studies ◽  
Cell Clones ◽  
Alpha Beta

Various aspects of the interferon (IFN) system were studied in malignant cells from 37 unselected patients with acute lymphocytic leukemia (ALL). It was found that leukemic cells from two of 37 patients had a complete loss of alpha- and beta-IFN genes, whereas cells from four of 37 had lost one of the alpha-/beta-IFN alleles. In 25 cases, viable cells were also available for functional studies. Cell clones with loss of one of the alpha-/beta-IFN alleles produced low amounts of IFN after virus induction in vitro. Some clones with an apparently normal set of IFN genes were unable to produce detectable amounts of IFN. All clones studied were found to carry high-affinity alpha-IFN receptors. In clones carrying deletions of IFN genes, the cells were sensitive to IFN in vitro as measured by alpha-IFN-induced enhancement of 2′,5′-oligoadenylate synthetase (2′,5′-A synthetase). Cells from four patients with an apparently normal set of IFN genes were insensitive to this effect of IFN. We conclude that of the 17 patients in which IFN genes, IFN production, alpha-IFN receptors, and IFN-induced enhancement of 2′,5′-A synthetase were studied, nine (53%) showed some abnormality in their IFN system. This finding may add some support to the hypothesis that defects in the IFN system could be a step on the path to malignant transformation in ALL. Moreover, patients whose malignant cells carry IFN gene deletions or other defects in their IFN-producing capacity, but are still sensitive to exogenous IFN, could represent a subgroup of ALL with a greater likelihood of responding to IFN therapy.

scholarly journals Interferon system in primary acute lymphocytic leukemia cells with or without deletions of the alpha-/beta-interferon genes

Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 2076-2083 ◽  
Author(s):  
D Grander ◽  
M Heyman ◽  
K Brondum-Nielsen ◽  
Y Liu ◽  
E Lundgren ◽  
...  
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Malignant Cells ◽  
Oligoadenylate Synthetase ◽  
Gene Deletions ◽  
Functional Studies ◽  
Cell Clones ◽  
Alpha Beta

Abstract Various aspects of the interferon (IFN) system were studied in malignant cells from 37 unselected patients with acute lymphocytic leukemia (ALL). It was found that leukemic cells from two of 37 patients had a complete loss of alpha- and beta-IFN genes, whereas cells from four of 37 had lost one of the alpha-/beta-IFN alleles. In 25 cases, viable cells were also available for functional studies. Cell clones with loss of one of the alpha-/beta-IFN alleles produced low amounts of IFN after virus induction in vitro. Some clones with an apparently normal set of IFN genes were unable to produce detectable amounts of IFN. All clones studied were found to carry high-affinity alpha-IFN receptors. In clones carrying deletions of IFN genes, the cells were sensitive to IFN in vitro as measured by alpha-IFN-induced enhancement of 2′,5′-oligoadenylate synthetase (2′,5′-A synthetase). Cells from four patients with an apparently normal set of IFN genes were insensitive to this effect of IFN. We conclude that of the 17 patients in which IFN genes, IFN production, alpha-IFN receptors, and IFN-induced enhancement of 2′,5′-A synthetase were studied, nine (53%) showed some abnormality in their IFN system. This finding may add some support to the hypothesis that defects in the IFN system could be a step on the path to malignant transformation in ALL. Moreover, patients whose malignant cells carry IFN gene deletions or other defects in their IFN-producing capacity, but are still sensitive to exogenous IFN, could represent a subgroup of ALL with a greater likelihood of responding to IFN therapy.

scholarly journals Serial In Vitro Bone Marrow Culture in Acute Lymphocytic Leukemia

Blood ◽  
1973 ◽  
Vol 42 (5) ◽  
pp. 687-699 ◽  
Author(s):  
M. J. Duttera ◽  
J. M. Bull ◽  
J. D. Northup ◽  
E. S. Henderson ◽  
E. D. Stashick ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphocytic Leukemia ◽  
Colony Growth ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Mean Values ◽  
Bone Marrow Cultures ◽  
The Mean ◽  
Nonlinear Fashion

Abstract Serial in vitro bone marrow cultures have been done on eight patients with acute lymphocytic leukemia. Colony-forming activity shows a rapid recovery from low values into the normal range in all patients who achieved stable remissions. Mean values for the stimulated cultures remained stable throughout consolidation, whereas the mean values for the unstimulated cultures declined during the same period. Relapse in two patients was preceded or accompanied by a concomitant decline in colony growth. Colony forming activity appears to be inhibited in a nonlinear fashion by increasing numbers of leukemic cells.

scholarly journals In vitro culture of leukemic cells in t(4;11) acute leukemia

Blood ◽  
1985 ◽  
Vol 66 (2) ◽  
pp. 439-443
Author(s):  
RC Stong ◽  
JH Kersey
Keyword(s):  
Acute Leukemia ◽  
Culture System ◽  
Acute Lymphocytic Leukemia ◽  
Chromosomal Translocation ◽  
Growth Characteristics ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Feeder Cells ◽  
Cloning Efficiency

In the present study we utilized a semisolid culture system with feeder cells and enriched media to evaluate the growth of acute leukemia associated with the 4;11 chromosomal translocation. We compared growth of t(4;11) leukemia to typical acute nonlymphocytic leukemia (ANL) and acute lymphocytic leukemia (ALL). The two cases of t(4;11) leukemia tested exhibited the highest cloning efficiency of cells tested. The growth characteristics of t(4;11) leukemia were more similar to ANL than ALL.

scholarly journals In vitro culture of leukemic cells in t(4;11) acute leukemia

Blood ◽  
1985 ◽  
Vol 66 (2) ◽  
pp. 439-443 ◽  
Author(s):  
RC Stong ◽  
JH Kersey
Keyword(s):  
Acute Leukemia ◽  
Culture System ◽  
Acute Lymphocytic Leukemia ◽  
Chromosomal Translocation ◽  
Growth Characteristics ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Feeder Cells ◽  
Cloning Efficiency

Abstract In the present study we utilized a semisolid culture system with feeder cells and enriched media to evaluate the growth of acute leukemia associated with the 4;11 chromosomal translocation. We compared growth of t(4;11) leukemia to typical acute nonlymphocytic leukemia (ANL) and acute lymphocytic leukemia (ALL). The two cases of t(4;11) leukemia tested exhibited the highest cloning efficiency of cells tested. The growth characteristics of t(4;11) leukemia were more similar to ANL than ALL.

scholarly journals A unique surface marker profile in T-cell acute lymphocytic leukemia

Blood ◽  
1980 ◽  
Vol 55 (4) ◽  
pp. 702-705
Author(s):  
ER Richie ◽  
MP Sullivan ◽  
J van Eys
Keyword(s):  
T Cell ◽  
Peripheral Blood ◽  
Acute Lymphocytic Leukemia ◽  
Early Stage ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Surface Marker ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Surface Marker Analysis

A 5-yr-old girl with acute lymphocytic leukemia presented with moderate hepatomegaly, marked splenomegaly, but no evidence of a mediastinal mass. The peripheral blood white count was 270 x 10(9)/liter with 99% leukemic cells. Surface marker analysis showed the lymphoblasts to be E- rosette negative and complement receptor positive. The patient's leukemic cells were unreactive with anti-p23,30, which detects Ia-like antigens, and strongly reactive with A99 anti-T-cell serum, which reacts with normal human thymocytes and peripheral blood T cells. The percentage of leukemic cells bearing complement receptors diminished during relapse. The leukemic cells obtained at diagnosis and during relapse were nonreactive to mitogens and alloantigens and failed to stimulate proliferation of normal lymphocytes in mixed lymphocyte culture. There was no evidence for active suppression of normal lymphocyte reactivity mediated by the leukemic cells. The surface marker and functional profile of these leukemic cells is consistent with that of an early stage in T-cell maturation.

scholarly journals Activation of the interleukin-3 gene by chromosome translocation in acute lymphocytic leukemia with eosinophilia [see comments]

Blood ◽  
1990 ◽  
Vol 76 (2) ◽  
pp. 285-289 ◽  
Author(s):  
TC Meeker ◽  
D Hardy ◽  
C Willman ◽  
T Hogan ◽  
J Abrams
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Chromosome Translocation ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
B Lineage ◽  
Stimulating Factor

Abstract The t(5;14)(q31;q32) translocation from B-lineage acute lymphocytic leukemia with eosinophilia has been cloned from two leukemia samples. In both cases, this translocation joined the IgH gene and the interleukin-3 (IL-3) gene. In one patient, excess IL-3 mRNA was produced by the leukemic cells. In the second patient, serum IL-3 levels were measured and shown to correlate with disease activity. There was no evidence of excess granulocyte/macrophage colony stimulating factor (GM-CSF) or IL-5 expression. Our data support the formulation that this subtype of leukemia may arise in part because of a chromosome translocation that activates the IL-3 gene, resulting in autocrine and paracrine growth effects.

scholarly journals Immune function at diagnosis in relation to responses to therapy in acute lymphocytic leukemia of childhood

Blood ◽  
1976 ◽  
Vol 47 (6) ◽  
pp. 1011-1021 ◽  
Author(s):  
DG Jose ◽  
H Ekert ◽  
J Colebatch ◽  
K Waters ◽  
F Wilson ◽  
...  
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Cranial Irradiation ◽  
Prophylactic Cranial Irradiation ◽  
Lymphocytic Leukemia ◽  
Lymphoid Cells ◽  
Multiple Drug ◽  
First Remission ◽  
Immune Capacity ◽  
Multiple Drug Therapy

Abstract Tests of immune capacity were performed on blood from 49 children with newly diagnosed, untreated acute lymphocytic leukemia, and relation to prognosis was determined. Patients were treated with multiple-drug therapy and prophylactic cranial irradiation. Median follow-up time was 16 mo (range 10--37 mo). Principal unfavorable findings at diagnosis were absolute numbers of T lymphoid cells outside the range 850-- 2500/mul blood, absence of whole blood responses to phytohemagglutinin in vitro, a low titer of complexed antibody, and the presence in serum of free leukemic blast cell membrane antigen. Fourteen patients showed two or more unfavorable findings at diagnosis. Eleven of these have died. Four of the remaining 35 patients have died. A shorter duration of first remission was found among patients with abnormal numbers of T cells at diagnosis. The findings suggest that the immunologic capacity of the patient at diagnosis is an important determinant in responses to therapy.

Aberrant expression of B-lymphocyte stimulator by B chronic lymphocytic leukemia cells: a mechanism for survival

Blood ◽  
2002 ◽  
Vol 100 (8) ◽  
pp. 2973-2979 ◽  
Author(s):  
Anne J. Novak ◽  
Richard J. Bram ◽  
Neil E. Kay ◽  
Diane F. Jelinek
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
B Lymphocyte ◽  
Leukemic Cell ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Aberrant Expression ◽  
B Lymphocyte Stimulator

B-cell chronic lymphocytic leukemia (B-CLL) is defined by the accumulation of CD5+ B cells in the periphery and bone marrow. This disease is not characterized by highly proliferative cells but rather by the presence of leukemic cells with significant resistance to apoptosis and, therefore, prolonged survival. B-lymphocyte stimulator (BLyS) is a newly identified tumor necrosis factor (TNF) family member shown to be critical for maintenance of normal B-cell development and homeostasis and it shares significant homology with another TNF superfamily member, APRIL. The striking effects of BLyS on normal B-cell maintenance and survival raises the possibility that it may be involved in pathogenesis and maintenance of hematologic malignancies, including B-CLL. In this study, we investigated the status of APRIL and BLyS expression, as well as their receptors, in this disease. All B-CLL patient cells studied expressed one or more of 3 known receptors for BLyS; however, the pattern of expression was variable. In addition, we demonstrate for the first time that B-CLL cells from a subset of patients aberrantly express BLyS and APRIL mRNA, whereas these molecules were not detectable in normal B cells. Furthermore, we provide in vitro evidence that BLyS protects B-CLL cells from apoptosis and enhances cell survival. Because these molecules are key regulators of B-cell homeostasis and tumor progression, leukemic cell autocrine expression of BLyS and APRIL may be playing an important role in the pathogenesis of this disease.

scholarly journals Primary leukemia cells resistant to alpha-interferon in vitro are defective in the activation of the DNA-binding factor interferon- stimulated gene factor 3

Blood ◽  
1994 ◽  
Vol 84 (6) ◽  
pp. 1942-1949 ◽  
Author(s):  
B Xu ◽  
D Grander ◽  
O Sangfelt ◽  
S Einhorn
Keyword(s):  
Close Correlation ◽  
Lymphocytic Leukemia ◽  
Alpha Interferon ◽  
Leukemia Cells ◽  
Blast Transformation ◽  
Oligoadenylate Synthetase ◽  
Binding Factor ◽  
Ifn Treatment ◽  
Possible Cause

Abstract Cells from one-third of chronic lymphocytic leukemia (CLL) patients are resistant to alpha-interferon (alpha-IFN) as measured by induction of blast transformation. We have previously shown that all CLL clones express alpha/beta-IFN receptors, but that the resistant cells are defective in the induction of the enzyme 2′,5′-oligoadenylate synthetase (2′,5-A synthetase). Thus, the deficiency in IFN sensitivity is localized somewhere between the interaction of the IFN molecule with its receptor and induction of 2′,5′-A synthetase. We have now further characterized the resistance of CLL clones to IFN by investigating whether it is associated with a defect in the activation of IFN- stimulated gene factor 3 (ISGF3), which is involved in the activation of alpha-IFN-stimulated genes (ISGs). A defect induction of ISGF3 after alpha-IFN treatment was found in 4 of 12 CLL patients. There was a close correlation between defective induction of ISGF3 and a lack of enhancement of 2′,5′-A synthetase as well as induction of blast transformation. Pretreatment with gamma-IFN and mixing experiments with extracts from IFN-sensitive cells indicate that a lack of the gamma- component of ISGF3 was the reason for defect in activation in 2 of the patients. We conclude that a defect in activation of ISGF3 is a possible cause for resistance in CLL cells to IFN-induced blast transformation in vitro.

scholarly journals High incidence of monoclonal proteins in the serum and urine of chronic lymphocytic leukemia patients

Blood ◽  
1984 ◽  
Vol 64 (6) ◽  
pp. 1207-1211 ◽  
Author(s):  
MJ Deegan ◽  
JP Abraham ◽  
M Sawdyk ◽  
EJ Van Slyck
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Membrane Immunoglobulin ◽  
High Incidence ◽  
Secretory Products ◽  
Monoclonal Proteins ◽  
Chain Type ◽  
Serum And Urine

Abstract Chronic lymphocytic leukemia (CLL) is generally considered a nonsecretory B cell immunoproliferative disorder. Conventional electrophoretic and immunoelectrophoretic methods have revealed serum monoclonal proteins in less than 10% of these patients. However, there is increasing experimental evidence from in vitro studies demonstrating that CLL cells may secrete immunoglobulins, particularly free light chains. We examined the serum and urine of 36 consecutive CLL patients for monoclonal proteins using sensitive immunochemical methods (high resolution agarose gel electrophoresis combined with immunofixation). The results obtained were correlated with the Rai stage, quantitative immunoglobulin levels, and lymphocyte membrane immunoglobulin phenotype of the leukemic cells. Twenty-three monoclonal proteins were identified in the serum or urine of 22 patients, an incidence of 61%. Six patients had serum monoclonal proteins, seven had only urinary monoclonal proteins, and nine had monoclonal proteins in serum and urine. In every instance the monoclonal protein was the same light chain type as expressed on the leukemic cells. Our findings suggest that the monoclonal proteins observed in the serum or urine of CLL patients are secretory products of the tumor cells and that their discovery is a function of the sensitivity of the method used for their detection.

Sign in / Sign up

Export Citation Format

Share Document