1991
DOI: 10.1007/bf00314980
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New synergistic combinations of differentiation inducing agents in the treatment of acute myeloid leukaemia

Abstract: Differentiation inducing agents in double and triple combinations can induce differentiation in primary culture of more than 80% of blast cells from some AML patients. In the present study, the interactions between these differentiating agents have been analysed using Berenbaum's general algebraic solution and three new, potentially clinically useful synergistic combinations: have been identified all trans retinoic acid (RA) + hexamethylene bisacetamide (HMBA), cytosine arabinoside (Ara-C) + HMBA and RA + Ara-… Show more

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Cited by 9 publications
(7 citation statements)
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“…However, tRA-induced differentiation in leukemia cells without the PML-RAR␣ product was also enhanced by HMBA, NaB, or other HDACI. [39][40][41][42] Thus, HMBA and NaB may also enhance tRA-induced differentiation by a pathway independent of PML-RAR␣ proteolysis. Another possibility is that the expression and functions of tRA-up-regulated genes are enhanced by these agents.…”
Section: Discussionmentioning
confidence: 99%
“…However, tRA-induced differentiation in leukemia cells without the PML-RAR␣ product was also enhanced by HMBA, NaB, or other HDACI. [39][40][41][42] Thus, HMBA and NaB may also enhance tRA-induced differentiation by a pathway independent of PML-RAR␣ proteolysis. Another possibility is that the expression and functions of tRA-up-regulated genes are enhanced by these agents.…”
Section: Discussionmentioning
confidence: 99%
“…Dose-response curves of the percentage of nitroblue tetrazolium dye reducing cells in relation to control cultures on day 4 were plotted versus the logarithm of concentrations of RA when used alone or in combinations with IL-6. EDSO values were Calculated from the logarithmic regression analysis of each doseresponse curve as described previously (Hassan & Maurer 1991). The dose reduction index indicates how many fold of dose reduction is needed to achieve a given effect in combination compared to the agent alone (Berman et al 1989).…”
Section: Calculation Of Edso and Dose Reduction Index Of Retinoic Acidmentioning
confidence: 99%
“…The dose reduction index indicates how many fold of dose reduction is needed to achieve a given effect in combination compared to the agent alone (Berman et al 1989). The dose reduction index was calculated by dividing the EDSO value for RA alone by the dose of RA required in combination with IL-6 to produce the same effect as described previously (Hassan & Maurer 1991).…”
Section: Calculation Of Edso and Dose Reduction Index Of Retinoic Acidmentioning
confidence: 99%
“…Several chemical and biological agents enhanced cytarabine activity in human myeloid leukaemia cells [7], Recombi nant human granulocyte-macrophage col ony stimulating factor (GM-CSF) not only enhanced vitamin D3-induced monocytic differentiation of U937 human monoblastic leukacmic cells [8] and rctinoic-acid-induced granulocytic differen tiation of human congenital agranulocy tosis bone marrow progenitor cells [9] but also the cytostatic activity of cytara bine and hydroxyurea in HL-60 [101 and AML [11,12] cells. Moreover, GM-CSF co-operated with cytarabine in inducing differentiation of the resistant human myeloid luekaemic cell line KG1 [13] and with recombinant human erythropoietin in inducing erythroid differentiation in more than 80% of K562 clonogenic cells [14], Recombinant human interlcukin-3 (IL-3) enhanced the cytoxicity of cytara bine in AML cells [12,15].…”
Section: Introductionmentioning
confidence: 99%
“…Moreover, GM-CSF co-operated with cytarabine in inducing differentiation of the resistant human myeloid luekaemic cell line KG1 [13] and with recombinant human erythropoietin in inducing erythroid differentiation in more than 80% of K562 clonogenic cells [14], Recombinant human interlcukin-3 (IL-3) enhanced the cytoxicity of cytara bine in AML cells [12,15]. Recombinant human interferons enhanced retinoicacid-, vitamin-Dr and tumour-necrosisfactor-a-induced growth inhibition and differentiation of human myeloid leukae mia cells [7].…”
Section: Introductionmentioning
confidence: 99%