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

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.

Blood ◽  
1985 ◽  
Vol 66 (2) ◽  
pp. 439-443 ◽  
Author(s):  
RC Stong ◽  
JH Kersey

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.


Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 2076-2083 ◽  
Author(s):  
D Grander ◽  
M Heyman ◽  
K Brondum-Nielsen ◽  
Y Liu ◽  
E Lundgren ◽  
...  

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.


Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 2076-2083
Author(s):  
D Grander ◽  
M Heyman ◽  
K Brondum-Nielsen ◽  
Y Liu ◽  
E Lundgren ◽  
...  

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.


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 ◽  
...  

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.


Blood ◽  
1971 ◽  
Vol 37 (5) ◽  
pp. 499-511 ◽  
Author(s):  
JAMES F. HOLLAND ◽  
HANSJOERG SENN ◽  
TARIT BANERJEE

Abstract Localized leukocyte mobilization into autologous serum consists almost entirely of normal appearing granulocytes in normal subjects as well as in patients with acute myelocytic (AML) and acute lymphocytic leukemia (ALL). Sharp reduction in mobilization and in clearance of granulocytes was seen in patients with untreated AML, independent of morphologic subclass, whereas this was not found in ALL. Recombination experiments with leukemic and nonleukemic sera did not reproduce or correct the defects in AML. Nearly normal mobilization and clearance occurred in the remission state. These data taken together suggest that mature granulocytes in florid AML may be mature leukemic cells.


1987 ◽  
Vol 61 (4) ◽  
pp. 271-281 ◽  
Author(s):  
Simon Townson ◽  
C. Connelly ◽  
A. Dobinson ◽  
R. Muller

ABSTRACTAn in vitro system for chemotherapeutic research using adult male Onchocerca gutturosa has been developed as a model for O. volvulus. Using a culture system consisting of medium MEM+10% heat inactivated foetal calf serum (IFCS)+LLCMK2 (monkey kidney) feeder cells in an atmosphere of 5% CO2 in air, we examined the effects of a range of antiparasitic drugs on worm motility. Ivermectin, levamisole, furapyrimidone, Mel W, chloroquine, metrifonate, flubendazole, amoscanate and the Ciba-Geigy compounds CGP 6140, CGP 20′376 and CGI 17658 either immobilized or significantly reduced motility levels at a concentration of 5x10−5M or less within a 7-day period. Worms were affected at very low concentrations by ivermectin (effective conc. to reduce motility levels to 50% of controls, 3.14x10−8M), levamisole (7.95x10−8M), CGP 6140 (8.87x10−9M) and CGP 20′376 (2.78x10−8M). Difficulties were experienced in accurately repeating the immotile endpoint for levamisole due to an inconsistent partial recovery of motility. Over a 7-day period diethylcarbamazine had little effect on motility levels, while suramin caused a slight increase in activity compared to controls at some timepoints. Subsequent experiments demonstrated some differences in drug efficacy depending on the presence or absence of serum and feeder cells in the culture system probably because of drug avidly binding to serum proteins. However, serum and cells were found to be essential ingredients of the culture system to maintain worms in good condition, indicating that new drugs should be evaluated both in the presence and absence of serum and cells. Comparisons were made between the responses of O. gutturosa and Brugia pahangi to certain drugs and these species were found to significantly differ in their sensitivities to ivermectin and a novel compound (Wellcome), indicating that Onchocerca parasites should be used wherever possible for compound identification and development intended for the treatment of onchocerciasis. The in vitro system described here, using male O. gutturosa, provides a basis for further research and a practical alternative to O. volvulus.


Blood ◽  
1973 ◽  
Vol 41 (2) ◽  
pp. 259-263 ◽  
Author(s):  
Elliott Hinkes ◽  
Barbara F. Crandall ◽  
Felice Weber ◽  
Charles G. Craddock

Abstract The occurrence of acute lymphocytic leukemia in a young man with a C-G translocation is described. Two members of his family also show C-G translocations but have not as yet developed leukemia. A third member of the family, on whom no chromosomal information was available, died of acute lymphocytic leukemia.


Blood ◽  
1980 ◽  
Vol 55 (4) ◽  
pp. 702-705
Author(s):  
ER Richie ◽  
MP Sullivan ◽  
J van Eys

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.


Blood ◽  
1990 ◽  
Vol 76 (2) ◽  
pp. 285-289 ◽  
Author(s):  
TC Meeker ◽  
D Hardy ◽  
C Willman ◽  
T Hogan ◽  
J Abrams

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.


Blood ◽  
1976 ◽  
Vol 47 (6) ◽  
pp. 1011-1021 ◽  
Author(s):  
DG Jose ◽  
H Ekert ◽  
J Colebatch ◽  
K Waters ◽  
F Wilson ◽  
...  

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.


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