No significant interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF), was detected in these patients demonstrating that a different pattern of growth factors secretion exist in AML and CML, where distinct molecular events are likely involved in the control of leukaemic proliferation.
This difference was reflected in the effectiveness of G-CSF to stimulate colony formation in acute myeloid leukemia blasts, while G-CSF did not stimulate colony formation of the blast cells from acute lymphoid leukemia.
The in vitro growth response of bone marrow and blood cells to granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) was studied in 18 acute myeloid leukemia (AML) patients using semisolid and suspension cultures.
We report: (i) that the respective position of the five genes is centromere - c-erbA-1 - G-CSF - c-erbB-2 - RAR alpha - MPO - telomere; (ii) that the breakpoints of the various AML subtypes are variably located between the centromere and c-erbB-2 in M1 and M2; (iii) that the breakpoints are consistently located between c-erbB-2 and RAR alpha/MPO in M3; and (iv) that the breakpoint on chromosome 17 in the 15;17 translocation is located on 17q21 and not on 17q11-12 as previously reported.
Incubation of blasts from three patients with AML in serum-free medium with TNF (10(3) U/ml), and subsequent binding studies using 125I-G-CSF reveal that TNF downregulates the numbers of G-CSF receptors by approximately 70%.
As acute myeloblastic leukemia (AML) blasts can express and produce hematopoietic growth factors, the influence of TNF-alpha on the accumulation of mRNAs for c-myc, interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, IL-6 and IL-1 beta was evaluated in fresh blasts from 13 patients with AML.
Only in one patient a complex rearrangement of the G-CSF gene with possible amplification was noted indicating rarity of direct alterations of growth factor genes in acute myelogenous leukemia (AML).
These results indicate that G-CSF may be sufficient to provide a specific signal for induction of a transient proliferation in AML without induction of terminal differentiation.
At high concentrations, DAB486-G-CSF is cytotoxic towards G-CSF-dependent OCI/AML1 cells, but not factor independent OCI/AML3 cells; colony formation by G-CSF-responsive leukemic blasts from a patient with acute myeloblastic leukemia (AML) was also inhibited.
The G-CSF-combined pretransplant conditioning regimen for ABSCT may be effective in the treatment of high-risk AML by increasing the chemosensitivity of the residual leukemic cells.
In poor prognosis acute myeloid leukemia (AML), the combination of fludarabine with Ara-C and granulocyte colony-stimulating factor (G-CSF) has proven to be a highly effective regimen.
Abnormalities in the signal-transduction pathways for granulocyte colony-stimulating factor (G-CSF) may play a part in the progression to acute myeloid leukemia.
Acute myeloblastic leukemia (ANLL-M2) with t(8;21)(q22;q22) variant expressing lymphoid but not myeloid surface antigens with a high number of G-CSF receptors.
Acute myeloid leukemia (AML) blast cells frequently produce interleukin-6 (IL-6) and other cytokines such as colony-stimulating factors (CSF: G-CSF, M-CSF, and GM-CSF), tumor necrosis factor (TNF)-alpha, and IL-1.
Intensive chemotherapy with idarubicin, cytosine arabinoside, and granulocyte colony-stimulating factor (G-CSF) in patients with secondary and therapy-related acute myelogenous leukemia. Club de Réflexion en Hématologie.
Recently, point mutations in the gene of the granulocyte colony-stimulating factor (G-CSF) receptor have been reported in two patients with severe congenital neutropenia who developed acute myeloid leukemia (AML).
Randomized clinical study comparing aggressive chemotherapy with or without G-CSF support for high-risk myelodysplastic syndromes or secondary acute myeloid leukaemia evolving from MDS.
These results explain the molecular basis for G-CSFR mutations in the pathogenesis of the dominant-negative phenotype and hypersensitivity to G-CSF in SCN/AML.
Expression of GIG-1 mRNA was elevated by treatment with G-CSF in normal bone marrow mononuclear cells, as well as in some cases of blast cells obtained from patients with acute myelogenous leukemia (AML) and CML.
Sustained receptor activation and hyperproliferation in response to granulocyte colony-stimulating factor (G-CSF) in mice with a severe congenital neutropenia/acute myeloid leukemia-derived mutation in the G-CSF receptor gene.
G-CSF distinctly promoted the proliferation of leukaemic cells of t(16;21) AML, but did not enhance the expression of MPO and neutrophil differentiation of these cells.