Growth regulation of human acute myeloid leukemia: effects of five recombinant hematopoietic factors in a serum-free culture system

Delwel, Ruud; Salem, Mohammad; Pellens, Carin; Dorssers, LC; Wagemaker, Gerard; Clark, Steven C.; Löwenberg, Bob

doi:10.1182/blood.v72.6.1944.bloodjournal7261944

Cited by 10 publications

(9 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The expression of blast cell colonies appears to be similar to findings observed in the blast cells of AML. Most leukemia cells depend on growth factors for proliferation, and GM-CSF as well as IL-3 were seen to be potent stimulating factors for blast cell proliferation but with lesser effects on differentiation (39)(40)(41)(42)(43). This may explain why several patients (Patients 8 and 16) showed increased colony formation with in v i m stimulation by GM-CSF or IL-3 alone in comparison with multiple growth factors (Fig.…”

Section: Discussionmentioning

confidence: 99%

Proliferation and differentiation of myelodysplastic CD34+ cells in serum‐free medium: II. Response to combined colony‐stimulating factors

Sawada

Sato

Notoya

et al. 1995

European J of Haematology

View full text Add to dashboard Cite

To investigate the role of colony stimulating factors (CSFs) in the proliferation and differentiation of progenitor cells from myelodysplastic syndromes (MDS), marrow progenitor cells from 18 MDS patients were highly purified using CD34 monoclonal antibody and immunomagnetic microspheres (MDS CD34+ cells). These cells were cultured in serum‐free medium with various combinations of five colony stimulating factors (CSFs): recombinant human interleukin‐3 (rIL‐3), granulocyte/macrophage‐CSF (rGM‐CSF), granulocyte‐CSF (rG‐CSF), macrophage‐CSF (rM‐CSF), and erythropoietin (rEP). Among the tested CSFs, such as rM‐CSF, rG‐CSF, rGM‐CSF and rIL‐3, a combination of the first three CSFs was the most effective stimulus for the proliferation of non‐erythroid MDS progenitor cells. An increase of undifferentiated “blast” cell colonies in 5/18 MDS patients occurred and these 5 patients belonged to the high‐risk group. In the presence of these three CSFs, rIL‐3 had no effect on the proliferation and differentiation of MDS CD34+ cells; however, IL‐3 was efficient for the proliferation of MDS CD34+ cells to the erythroid lineage. rGM‐CSF or rIL‐3 alone did not efficiently support proliferation and differentiation of CD34+ cells. M‐CSF is present in normal human serum at a concentration of 550 ±110 U/ml, a concentration exceeding that used in this study (100 U/ml). Therefore, in vivo administration of G‐CSF combined with GM‐CSF to MDS patients may be one of the most effective CSF combinations for proliferation of MDS progenitor cells to the non‐erythroid lineage. However, the effect on the capacity for differentiation was minimal, especially in patients belonging to the high‐risk group.

show abstract

Section: Discussionmentioning

confidence: 99%

Proliferation and differentiation of myelodysplastic CD34+ cells in serum‐free medium: II. Response to combined colony‐stimulating factors

Sawada

Sato

Notoya

et al. 1995

European J of Haematology

View full text Add to dashboard Cite

show abstract

“…The growth of leukaemic cells also depends on cytokines in vitro. G-CSF and GM-CSF were shown to promote proliferation of leukaemic cells in 50% of peripheral blood or bone marrow samples isolated from patients with AML (Delwel et al, 1987(Delwel et al, , 1988Vellenga et al, 1987). A combination of SCF and other cytokines provided a growth advantage to CD34positive leukaemic cells obtained from MDS patients (Sawada et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Effect of cytokines on growth and differentiation of leukaemic cells with translocation t(6;9)(p23;q34)

et al. 2001

View full text Add to dashboard Cite

Summary. The translocation t(6;9)(p23;q34) is detected infrequently in subtypes of haematological malignancies including acute myelogenous leukaemia (AML) and myelodysplastic syndrome (MDS). Although the t(6;9) leukaemia is commonly associated with bone marrow basophilia, the cytological characteristics of leukaemic cells are unclear. In the current study, we examined the in vitro effects of several cytokines on growth and differentiation of t(6;9) leukaemic cells. Isolated bone marrow mononuclear cells from four patients with t(6;9) (two MDS and two AML) were cultured for 14 d in the presence or absence of each cytokine. At the end of culture, viable cells were counted, and their histology was examined. Bone marrow cells obtained from 22 patients (10 AML, six AML from MDS, six MDS) lacking t(6;9) were used as controls. Compared with control cultures, significantly higher numbers of blasts appeared in the culture of bone marrow cells from t(6;9)-positive patients in response to stimulation with granulocyte colony-stimulating factor (G-CSF), granulocyte±macrophage CSF (GM-CSF) or interleukin 3 (IL-3). Stem cell factor (SCF) had little effect. Neutrophil counts were also significantly increased in the presence of G-CSF or IL-3. SCF and IL-3 were potent in increasing basophil counts from t(6;9)-positive cultures. These findings suggest that bone marrow cells obtained from t(6;9) patients are highly sensitive to growth-and/or differentiation-promoting cytokines. Special attention should be paid to the use of`therapeutic' cytokines in these patients.

show abstract

“…DNA synthesis assay. DNA synthesis was assessed by uptake of 3 H-thymidine ( 3 H-TdR, specific activity 2 Ci/mmol, Amersham International, Amersham) as described (Delwel et al, 1988). In brief, 0 .…”

Section: Methodsmentioning

confidence: 99%

CD20 and CD40 mediated mitogenic responses in B‐lineage acute lymphoblastic leukaemia

Smiers

Paassen²,

Hählen

et al. 1996

Br J Haematol

View full text Add to dashboard Cite

Activation of CD20, a cross-membrane ion channel, induces cell cycle progression from G0 to G1 in B lymphocytes. Subsequent activation of CD40, a membrane receptor of the nerve growth factor receptor superfamily, transits the B cells to the S phase. CD40 may also act synergistically in combination with IL-4 (B lymphocytes) or IL-3/IL-7 (B-cell precursors). We investigated the proliferative responses of B-lineage acute lymphoblastic leukaemia (ALL) cells to CD20/CD40 activation. In 18/56 ALL cases, CD20 activation resulted in significant increases in DNA synthesis. Similar, although more moderate, effects were seen of activation of CD40 in 10/44 cases. Responses to CD20 or CD40 activation were independent of co-stimulation with IL-3, IL-4 or IL-7, and various cocktails of the different growth stimuli did not act synergistically.

show abstract

Growth regulation of human acute myeloid leukemia: effects of five recombinant hematopoietic factors in a serum-free culture system

Cited by 10 publications

References 0 publications

Proliferation and differentiation of myelodysplastic CD34+ cells in serum‐free medium: II. Response to combined colony‐stimulating factors

Proliferation and differentiation of myelodysplastic CD34+ cells in serum‐free medium: II. Response to combined colony‐stimulating factors

Effect of cytokines on growth and differentiation of leukaemic cells with translocation t(6;9)(p23;q34)

CD20 and CD40 mediated mitogenic responses in B‐lineage acute lymphoblastic leukaemia

Contact Info

Product

Resources

About