|
Leukemia, Myelocytic, Acute
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
We have investigated the regulation of expression of GM-CSF in AML cell lines, and our results demonstrate the presence of a strong constitutive promoter element contained within 53 bp upstream of the cap site.
|
8114751 |
1994 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
Biomarker
|
disease |
BEFREE |
In this study, we wished to investigate for the presence of such intracellular loops involving GM-CSF in AML blast cells.
|
7516889 |
1994 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
Biomarker
|
disease |
BEFREE |
We have previously shown that blasts from some patients with acute myeloblastic leukaemia (AML) grow autonomously in vitro and that this growth pattern is related to the production of autocrine growth factors including granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-1 beta.
|
8043435 |
1994 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
Biomarker
|
disease |
BEFREE |
Blast cells from up to 70% of patients with acute myeloblastic leukemia (AML) exhibit a variable degree of autonomous growth in vitro which is related to the production of autocrine growth factors including granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 (IL-1) and interleukin-6 (IL-6).
|
7967742 |
1994 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
Biomarker
|
disease |
BEFREE |
Since retroviral infection of the human GM-CSF dependent cell line, TF-1, leads to factor independent growth by increased expression of the GM-CSF receptor alpha chain in a subgroup of infected clones, we were interested in studying the role of this chain in human AML.
|
7845015 |
1995 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
The beta subunit common to the GM-CSF, IL-3 and IL-5 receptors is highly polymorphic but pathogenic point mutations in patients with acute myeloid leukaemia (AML) are rare.
|
8558916 |
1996 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
Biomarker
|
disease |
BEFREE |
Mononuclear BM cells from patients with newly diagnosed AML were cultured in serum-free conditions with flt3-L, SCF, granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage-colony-stimulating factor (GM-CSF) alone and in combination.
|
8916965 |
1996 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
Biomarker
|
disease |
BEFREE |
Regulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors in a GM-CSF-dependent human myeloid leukemia cell line (AML-193) by interleukin-6.
|
8641372 |
1996 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
Biomarker
|
disease |
BEFREE |
Activity of thymidine kinase and of polymerase alpha as well as activity and gene expression of deoxycytidine deaminase in leukemic blasts are correlated with clinical response in the setting of granulocyte-macrophage colony-stimulating factor-based priming before and during TAD-9 induction therapy in acute myeloid leukemia.
|
9292531 |
1997 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
Biomarker
|
disease |
BEFREE |
Since DTctGMCSF enters and kills its target cells by unique mechanisms (GMCSF-receptor binding and protein synthesis inhibition) and is not similar in structure to Pgp or MRP substrates, we postulated that it would be an active agent against therapy-resistant AML.
|
9168435 |
1997 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
Biomarker
|
disease |
BEFREE |
Therefore, binding and internalization of GM-CSF probably occur in immature AML precursors of these two cases of AML.
|
9345060 |
1997 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
Biomarker
|
disease |
BEFREE |
We conclude that DT388-GM-CSF can kill acute myeloid leukemia blasts but that apoptotic sensitivities will depend on the presence of at least 100 high affinity GM-CSF receptors/cell and the absence of overexpressed antiapoptotic proteins.
|
9345050 |
1997 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
Biomarker
|
disease |
BEFREE |
A novel GM-CSF-dependent myeloid cell line, OHN-GM, was established from a patient who developed acute myelogenous leukaemia (AML) as a consequence of myelodysplastic syndrome (MDS).
|
9266938 |
1997 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
We have used genetic engineering based on the elucidated molecular structures of human granulocyte-macrophage colony-stimulating factor and diphtheria toxin (DT) to produce a recombinant fusion toxin, DTctGMCSF, that targets diphtheria toxin to high affinity GMCSF receptors expressed on the surface of blast cells from a large fraction of patients with acute myeloid leukemia (AML).
|
9168436 |
1997 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
Biomarker
|
disease |
BEFREE |
Under the same conditions of exposure, normal hematopoietic progenitors are relatively unaffected by DT388-GMCSF, suggesting its potential as a therapeutic agent in AML.
|
9657759 |
1998 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
Biomarker
|
disease |
BEFREE |
Previous work using DTctGMCSF produced in Escherichia coli has shown that this chimeric toxin is selectively cytotoxic to GMCSF receptor (R)-positive acute myeloid leukemia (AML) cells both in vitro and in vivo.
|
9675065 |
1998 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
Biomarker
|
disease |
BEFREE |
Activating point mutations in the betaC chain of the GM-CSF, IL-3 and IL-5 receptors are not a major contributory factor in the pathogenesis of acute myeloid leukaemia.
|
9792291 |
1998 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
Biomarker
|
disease |
BEFREE |
These results suggest that GM-CSF-independent growth of AML cells is associated with overexpression of MDM2 protein and related modulation of p53 expression.
|
9680365 |
1998 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
Biomarker
|
disease |
BEFREE |
Although adenoviruses can infect nondividing cells, we observed that a combination of growth factors (GM-CSF, IL-3, stem cell factor) was required for efficient transduction in order to maintain AML blast cell viability.
|
10435081 |
1999 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
Biomarker
|
disease |
BEFREE |
In AML cultures with GM-CSF and TNFalpha, coexpression of CD80 and either CD34 or an aberrant surface marker (CD56) was seen.
|
10720135 |
2000 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
We also found that GM-CSF induced the expression of RAR alpha in blood cells obtained from patients with acute myeloid leukemia.
|
10969805 |
2000 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
Biomarker
|
disease |
BEFREE |
Sera from 43 patients with AML were tested by bioassay and a specific enzymoimmunoassay (EIA) for anti-DT-GM antibodies.
|
11465948 |
2001 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
Biomarker
|
disease |
BEFREE |
Phase I trial of a novel diphtheria toxin/granulocyte macrophage colony-stimulating factor fusion protein (DT388GMCSF) for refractory or relapsed acute myeloid leukemia.
|
12006512 |
2002 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
However, G-CSF, but not GM-CSF and IL-3, enhanced clonal growth in three cases of high risk patients with MDS (RAEB, RAEB-t, and MDS having progressed to acute myeloid leukemia (AML)) and one low risk patient (RA).
|
12012328 |
2002 |
|
Leukemia, Myelocytic, Acute
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
In some cases, endogenous GM-CSF expression by transduced AML cells induced phenotypic changes consistent with the maturation of leukemia blasts into antigen-presenting cells.
|
12200676 |
2002 |