Bortezomib activity and in vitro interactions with anthracyclines and cytarabine in acute myeloid leukemia cells are independent of multidrug resistance mechanisms and p53 status

2006 ◽  
Vol 60 (2) ◽  
pp. 245-255 ◽  
Author(s):  
Hans Minderman ◽  
Yunfei Zhou ◽  
Kieran L. O’Loughlin ◽  
Maria R. Baer
Keyword(s):  
Acute Myeloid Leukemia ◽  
Multidrug Resistance ◽  
Myeloid Leukemia ◽  
Resistance Mechanisms ◽  
Leukemia Cells ◽  
Acute Myeloid Leukemia Cells ◽  
P53 Status ◽  
Acute Myeloid ◽  
In Vitro Interactions

scholarly journals Oridonin induces NPM mutant protein translocation and apoptosis in NPM1c+ acute myeloid leukemia cells in vitro

2014 ◽  
Vol 35 (6) ◽  
pp. 806-813 ◽  
Author(s):  
Fei-fei Li ◽  
Sha Yi ◽  
Lu Wen ◽  
Jing He ◽  
Li-jing Yang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Protein Translocation ◽  
Leukemia Cells ◽  
Mutant Protein ◽  
Acute Myeloid Leukemia Cells ◽  
Acute Myeloid

NEI-01-induced arginine deprivation has potent activity against acute myeloid leukemia cells both in vitro and in vivo

2021 ◽  
pp. molcanther.0120.2021
Author(s):  
Yun-Chung Leung ◽  
Yijun Cai ◽  
Jeremy P. H. Chow ◽  
Yu-On Leung ◽  
Xiaoxu Lu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Leukemia Cells ◽  
Arginine Deprivation ◽  
Acute Myeloid Leukemia Cells ◽  
Acute Myeloid

Multidrug resistance protein attenuates gemtuzumab ozogamicin–induced cytotoxicity in acute myeloid leukemia cells

Blood ◽  
2003 ◽  
Vol 102 (4) ◽  
pp. 1466-1473 ◽  
Author(s):  
Roland B. Walter ◽  
Brian W. Raden ◽  
Tom C. Hong ◽  
David A. Flowers ◽  
Irwin D. Bernstein ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Multidrug Resistance ◽  
Myeloid Leukemia ◽  
Resistance Mechanisms ◽  
Gemtuzumab Ozogamicin ◽  
Multidrug Resistance Protein ◽  
Acute Myeloid Leukemia Cells ◽  
Additional Resistance ◽  
Resistance Protein ◽  
Acute Myeloid

Abstract Gemtuzumab ozogamicin (GO) is a novel immunoconjugate therapy for acute myeloid leukemia (AML). P-glycoprotein (Pgp) confers resistance to GO and is associated with a worse clinical response. To address whether multidrug resistance protein (MRP) affects GO susceptibility, we characterized Pgp, MRP1, and MRP2 expression in CD33+ cell lines and CD33+ AML samples and analyzed the effect of the Pgp inhibitor cyclosporine (CSA) and the MRP inhibitor MK-571 on GO-induced cytotoxicity. MRP1, but not MRP2, expression correlated with MRP activity. MK-571 enhanced GO-induced cytotoxicity in Pgpnegative/MRP-positive NB4 and HL-60 cells. CSA, but not MK-571 alone, restored GO susceptibility in Pgp-positive/MRP-positive TF1 cells; however, MK-571 enhanced cytotoxicity in the presence of CSA. All patient samples exhibited MRP activity, and 17 of 23 exhibited Pgp activity. CSA increased GO-induced cytotoxicity in 12 Pgp-positive samples, whereas MK-571 alone was effective in only one sample with minimal Pgp activity. In 3 Pgp-positive/MRP-positive samples, MK-571 enhanced GO-induced cytotoxicity in the presence of CSA. Thus, MRP1 may attenuate susceptibility to GO. This effect was comparatively less than that for Pgp and required the inhibition of Pgp for detection in cells that coexpressed both transporters. Because MK-571 and CSA failed to affect cytotoxicity in a portion of Pgp-positive/MRP-positive AML samples, additional resistance mechanisms are likely important.

Rig-I Activates Expression of Interferon-Stimulated Genes (ISGs) and Inhibits the Proliferation of Acute Myeloid Leukemia Cells

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2846-2846 ◽  
Author(s):  
Nan-Nan Zhang ◽  
Lei Chen ◽  
Wu Zhang ◽  
Xian-Yang Li ◽  
Lin-Jia Jiang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Leukemia Cells ◽  
Mrna Levels ◽  
Terminal Part ◽  
Granulocytic Differentiation ◽  
Acute Myeloid Leukemia Cells ◽  
Acute Myeloid

Abstract Acute promyelocytic leukemia (APL) is initiated by the formation of PML/RARα oncogenic fusion protein, a potent transcriptional repressor. Retinoid acid (RA) at pharmacological dosage can physically bind to the PML/RARα protein, ushering in the unfolding of downstream programs normally regulated by the wild type RARα. However, through what particular regulatory pathways RA inhibits APL malignant hematopoiesis has remained largely obscured. Rig-I is one of the genes whose mRNA levels were highly up-regulated, along with all-trans-RA (ATRA)-induced terminal granulocytic differentiation of APL cell line NB4 cells in vitro. Based on the analysis of a Rig-I−/− mouse model, recently we have reported a critical regulatory role of Rig-I in normal granulopoiesis. To understand the functional contribution of Rig-I induction in RA-mediated leukemia cell differentiation, we converted a pair of previously reported Rig-I RNAi-duplex sequences into a miR30a-based small hairpin-encoding sequence, which was expressed under the CMV enhancer/promoter within a lentiviral vector. As expected, Rig-I shRNAmir30 infection induced a significant knockdown of Rig-I protein level, and accordingly its delivery into HL-60 cells partially inhibited ATRA-induced granulocytic differentiation, growth inhibition/cell cycle arrest and apoptosis induction, suggesting that Rig-I upregulation participates in RA-induced granulocytic differentiation of acute myeloid leukemia cells. In order to investigate the effect of Rig-I induction on the proliferation of APL cells in vivo, we transduced PML/RARα-harboring leukemic cells with vector or Rig-I-expressing retrovirus, and then transplanted these cells into the syngeneic mice. The vector-transduced APL cells readily expanded in vivo, but the proliferation of Rig-I-transduced cells was apparently prohibited. Moreover, we found that the forced expression of Rig-I induced the expression of numerous ISGs in APL cells, which was recapitulated by the transduction of the C terminal part of Rig-I, but not by the N terminal part. In line with this, during the in vitro short-term culture post-IFNγ or IFNα stimulation, Stat1 phosphorylation at p701 in Rig-I−/− granulocytes was significantly inhibited. In parallel, the induction of multiple ISGs by IFNs was also significantly impaired. In conclusion, our findings indicate that the Rig-I induction inhibited APL reconstitution potentially through up-regulating a number of ISGs via regulating Stat1Tyr701 phosphorylation.

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