Alterations of differentiation, clonal proliferation, cell cycle progression and bcl-2 expression in RARα-altered sublines of HL-60

Abstract

All-trans retinoic acid (RA) induces granulocytic differentiationbind all-trans RA as well as 9-cis RA, while RXRs bind only of acute promyelocytic leukemia cells both in vivo and in vitro.9-cis RA. [19][20][21] Thus, RARs heterodimerize to form RAR/RXR sociated from induction of differentiation and/or apoptosis of

Novel vitamin D3 analog, 21-(3-methyl-3-hydroxy-butyl)-19-nor D3, that modulates cell growth, differentiation, apoptosis, cell cycle, and induction of PTEN in leukemic cells

“…Several studies suggested that growth inhibition by 1,25(OH) 2 D 3 may be attributed to inhibition of the G 1 to S transition in the cell cycle, which probably is due at least in part to stimulation of expression of the cyclin-dependent kinase inhibitors (CDKIs), p21 waf1 and p27 kip1 as well as induction of programmed cell death. [1][2][3][4] In a clinical study, oral administration of 1,25(OH) 2 D 3 to preleukemic patients was only partially effective 5 ; calcemic side effects prevented the administration of the dosage of the compound needed to achieve the concentration of 1,25(OH) 2 D 3 in vivo, which was known to be necessary from our in vitro studies. 5,6 Therefore, synthesis of vitamin D 3 analogs with potent antiproliferative and differentiation activity against cancer cells with decreased risk of hypercalcemia has received considerable attention.…”

Blast maturity and CD34 expression determine the effects of the differentiating agents KH1060 and 9-cis-retinoic acid on the differentiation and clonogenicity of non-M3 acute myeloid leukaemia cells

“…6,9,11,[20][21][22] However, one drug resistant HL60 subline underwent differentiation without loss of bcl-2 protein 31 and transfection of bcl-2 does not inhibit differentiation. 19 Using flow cytometric protein measurement in conjunction with cell cycle analysis, we were able to examine protein expression on G0/G1 cells, thus ruling out the generalised protein loss of cell decay.…”

“…Ligation of this receptor is known to induce differentiation in leukemic cell lines. 6 In combination with other agents ATRA has also been found to inhibit the growth of non-APL (non-M3) AML blasts in vitro. 7,8 A number of retinoid and vitamin D analogues have been synthesized in recent years in the search for compounds which target malignant cell differentiation and apoptosis with minimal toxic effects on other systems.…”

“…[16][17][18][19] Bcl-2 is downregulated in leukaemic cells treated with differentiating agents, 6,9,11,[20][21][22][23] and this mechanism may underlie the increased sensitivity of leukaemic cells to the combination of cytotoxic drugs and ATRA. 17 In this study, we have therefore investigated the expression of bcl-2, and also bcl-x and bax, in AML cells treated with KH1060 and 9 cRA.…”

Bcl-2, bax and bcl-xL expression in human sensitive and resistant leukemia cell lines

“…Bcl-2 is normally expressed in human B lymphocytes, 26 but physiological expression is not restricted to B cells because hematopoietic precursors of all lineages express bcl-2. Independent of t(14;18) translocation bcl-2 dysregulation has been observed in several hematologic malignancies, such as chronic lymphoblastic leukemia, 27 acute myelogenous leukemia, [28][29][30][31][32][33][34][35] acute lymphoblastic leukemia and [36][37][38] lymphomas. [39][40][41] The common element of bcl-2 family members is amino acid homologies in the binding domains BH1 and BH2.…”