scholarly journals Cytoplasm Prepared from All-trans Retinoic Acid (ATRA)-Treated Human Hematopoietic Progenitor Cells Induces Differentiation of Both ATRA Sensitive and ATRA Resistant Leukemia Cells

2004 ◽  
Vol 27 (4) ◽  
pp. 570-573
Author(s):  
Hongjun Zhang ◽  
Zhao Wang ◽  
Jiangbing Zhou
Keyword(s):  
Retinoic Acid ◽  
Progenitor Cells ◽  
Hematopoietic Progenitor Cells ◽  
Leukemia Cells ◽  
Hematopoietic Progenitor ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

scholarly journals All-trans retinoic acid directly inhibits granulocyte colony- stimulating factor-induced proliferation of CD34+ human hematopoietic progenitor cells

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 2940-2945 ◽  
Author(s):  
EB Smeland ◽  
L Rusten ◽  
SE Jacobsen ◽  
B Skrede ◽  
R Blomhoff ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Colony Formation ◽  
Hematopoietic Progenitor Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Progenitor ◽  
Gm Csf ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Stimulating Factor

In this study we examine the effects of retinoids on purified CD34+ human hematopoietic progenitor cells. All-trans retinoic acid inhibited granulocyte colony-stimulating factor (G-CSF)-induced proliferation of CD34+ cells in short-term liquid cultures in a dose-dependent fashion with maximal inhibition of 72% at a concentration of retinoic acid of 1 mumol/L. Although no significant effects were observed on granulocyte- macrophage CSF (GM-CSF)--interleukin-3--or stem cell factor (SCF)- induced proliferation, the combinations of G-CSF and each of these cytokines were all inhibited. Moreover, retinol (3 mumol/L) and chylomicron remnant retinyl esters (0.1 mumol/L) in concentrations normally found in human plasma also had inhibitory effects. Single-cell experiments showed that the effects of retinoic acid were directly mediated. Retinoids also significantly inhibited G-CSF-induced colony formation in semisolid medium, with 88% inhibition observed at a concentration of retinoic acid of 1 mumol/L. However, we did not observe any effects of retinoic acid on G-CSF-induced differentiation as assessed by morphology and flowcytometry. Similar to previous findings using total bone marrow mononuclear cells, we observed a stimulation of GM-CSF-induced colony formation after 14 days. We also observed a stimulatory effect of low doses of retinoic acid (30 nmol/L) on blast-cell colony formation on stromal cell layers. Taken together, the data indicate that vitamin A present in human plasma has inhibitory as well as stimulatory effects on myelopoiesis.

scholarly journals All-trans retinoic acid directly inhibits granulocyte colony- stimulating factor-induced proliferation of CD34+ human hematopoietic progenitor cells

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 2940-2945 ◽  
Author(s):  
EB Smeland ◽  
L Rusten ◽  
SE Jacobsen ◽  
B Skrede ◽  
R Blomhoff ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Colony Formation ◽  
Hematopoietic Progenitor Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Progenitor ◽  
Gm Csf ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Stimulating Factor

Abstract In this study we examine the effects of retinoids on purified CD34+ human hematopoietic progenitor cells. All-trans retinoic acid inhibited granulocyte colony-stimulating factor (G-CSF)-induced proliferation of CD34+ cells in short-term liquid cultures in a dose-dependent fashion with maximal inhibition of 72% at a concentration of retinoic acid of 1 mumol/L. Although no significant effects were observed on granulocyte- macrophage CSF (GM-CSF)--interleukin-3--or stem cell factor (SCF)- induced proliferation, the combinations of G-CSF and each of these cytokines were all inhibited. Moreover, retinol (3 mumol/L) and chylomicron remnant retinyl esters (0.1 mumol/L) in concentrations normally found in human plasma also had inhibitory effects. Single-cell experiments showed that the effects of retinoic acid were directly mediated. Retinoids also significantly inhibited G-CSF-induced colony formation in semisolid medium, with 88% inhibition observed at a concentration of retinoic acid of 1 mumol/L. However, we did not observe any effects of retinoic acid on G-CSF-induced differentiation as assessed by morphology and flowcytometry. Similar to previous findings using total bone marrow mononuclear cells, we observed a stimulation of GM-CSF-induced colony formation after 14 days. We also observed a stimulatory effect of low doses of retinoic acid (30 nmol/L) on blast-cell colony formation on stromal cell layers. Taken together, the data indicate that vitamin A present in human plasma has inhibitory as well as stimulatory effects on myelopoiesis.

scholarly journals Regulation of myeloblastin messenger RNA expression in myeloid leukemia cells treated with all-trans retinoic acid

Blood ◽  
1993 ◽  
Vol 81 (2) ◽  
pp. 475-481 ◽  
Author(s):  
C Labbaye ◽  
J Zhang ◽  
JL Casanova ◽  
M Lanotte ◽  
J Teng ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Mrna Expression ◽  
Messenger Rna ◽  
Myeloid Leukemia ◽  
Leukemia Cell ◽  
Leukemia Cells ◽  
Human Leukemia ◽  
Nb4 Cells ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract Retinoic acid is known to induce differentiation of human myeloid leukemia cells in vitro. Recently, all-trans retinoic acid has been used to induce remissions in patients with acute promyelocytic leukemia, probably through differentiation of the leukemia cells. Myeloblastin (mbn) is a protease that has been identified in the human leukemia cell line HL-60. Downregulation of this protease can inhibit proliferation and induce differentiation of HL-60-derived leukemia cells. Here we have investigated the regulation of mbn messenger RNA (mRNA) expression in two human leukemia cell lines, HL-60 and NB4, treated with all-trans retinoic acid. Under this treatment, downregulation of mbn mRNA was observed in both cell lines, but was considerably delayed in NB4 cells that carry the t(15;17) translocation characteristic of acute promyelocytic leukemia. We have found that multiple mechanisms were involved in the control of mbn mRNA expression. These mechanisms were different in HL-60 and NB4 cells. Our results show that in HL-60 cells, all-trans retinoic acid rapidly decreased transcription of mbn. In contrast, in the t(15;17)-positive NB4 cells treated with all-trans retinoic acid, upregulation of mbn mRNA expression was followed by a late downregulation, both achieved via posttranscriptional mechanisms.

scholarly journals Differential effect of 4-hydroperoxycyclophosphamide and antimyeloid monoclonal antibodies on T and natural killer cells during bone marrow purging

Blood ◽  
1994 ◽  
Vol 83 (8) ◽  
pp. 2345-2351 ◽  
Author(s):  
RK Zhong ◽  
AD Donnenberg ◽  
J Rubin ◽  
ED Ball
Keyword(s):  
Bone Marrow ◽  
Monoclonal Antibodies ◽  
Natural Killer ◽  
Progenitor Cells ◽  
Interleukin 2 ◽  
Lymphoid Cells ◽  
Hematopoietic Progenitor Cells ◽  
Leukemia Cells ◽  
High Dose ◽  
Hematopoietic Progenitor

Abstract Autologous bone marrow (BM) transplantation after high dose therapy is widely used to treat acute leukemia, lymphoma, and selected solid tumors. In studies of BM purging with chemical agents, monoclonal antibodies (MoAbs), or other agents, the emphasis has been on the efficacy of tumor cell removal and sparing of hematopoietic progenitor cells. Two commonly used methods of BM purging for patients with acute myeloid leukemia have been the drug 4-hydroperoxycyclophosphamide (4- HC) and (MoAbs) directed to myeloid antigens such as CD14, CD15, and CD33. Although both methods of BM purging have potent activity against leukemia cells, 4-HC is also quite toxic to normal hematopoietic progenitor cells in the same concentrations that are used to deplete leukemia cells. To further characterize the cellular composition of BM after purging, we examined the effects of MoAbs plus complement and 4- HC on cells of the lymphoid lineage in the BM. 4-HC exerted a concentration-dependent cytotoxicity on clonogenic T lymphocytes, natural killer (NK) cells, and lymphokine (interleukin-2)-activated killer (LAK) cells, whereas the anti-CD14 and anti-CD15 MoAbs had little effect. At a concentration of 4-HC commonly used for BM purging (60 micrograms/mL), there were 4 to 5 logs of T-cell depletion and almost complete elimination of NK- and LAK-cell activity. In contrast, 4-HC at low concentrations (eg, 3 micrograms/mL) spared the majority of lymphoid cells suggesting that low concentration 4-HC combined with MoAb purging may be a desirable alternative to higher concentration 4- HC. These data indicate that purging with antimyeloid MoAbs, but not with 4-HC, spares the function of mature graft lymphocytes. Infusion of viable lymphocytes may be important for the transfer of immune memory against microbial and neoplastic antigens and may hasten immune reconstitution. In addition, mature graft lymphocytes may also be selectively activated and expanded in conjunction with interleukin-2 administration after BM transplantation.

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