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

Multidrug Resistance Protein (MRP) Attenuates Gemtuzumab Ozogamicin-Induced Cytotoxicity In Acute Myeloid Leukemia Cells Running head: MRP attenuates GO-induced cytotoxicity

Multidrug-resistance phenotype and clinical responses to gemtuzumab ozogamicin.

Expression of multidrug resistance (MDR) features by acute myeloid leukemia (AML) cells predicts a poor response to many treatments. The MDR phenotype often correlates with expression of P-glycoprotein (Pgp), and Pgp antagonists such as cyclosporine (CSA) have been used as chemosensitizing agents in AML. Gemtuzumab ozogamicin, an immunoconjugate of an anti-CD33 antibody linked to calicheamicin,...

The peripheral benzodiazepine receptor ligand PK11195 overcomes different resistance mechanisms to sensitize AML cells to gemtuzumab ozogamicin.

The antibody-targeted therapeutic, gemtuzumab ozogamicin (GO, Mylotarg), is approved for treatment of relapsed acute myeloid leukemia (AML). We previously showed that AML blasts from GO refractory patients frequently express the drug transporters P-glycoprotein (Pgp) and/or multidrug resistance protein (MRP). We also previously reported that inhibition of drug transport by the Pgp modulator, cy...

Treatment of a Child with Refractory Acute Myeloid Leukemia with Humanized Anti-CD33 Monoclonal Antibody: A Case Report and Review of Drug Development

Background: The induction chemotherapy regimen for acute myeloid leukemia has evolved as once induction is completed patients progress through the consolidation phase and achieve remission in 76% of cases. For patients with relapsed or refractory disease, alternative chemotherapy agents are available. Monoclonal antibody therapy with biological agents, such as the immunotoxin gemtuzumab ozog...

Influence of CD33 expression levels and ITIM-dependent internalization on gemtuzumab ozogamicin-induced cytotoxicity.

Gemtuzumab ozogamicin (GO; Mylotarg), a novel immunoconjugate used for treatment of acute myeloid leukemia (AML), contains the humanized anti-CD33 antibody (hP67.6) as a carrier to facilitate cellular uptake of the toxic calicheamicin-gamma(1) derivative. By use of lentivirus-mediated gene transfer to manipulate CD33 expression in myeloid cell lines that normally lack CD33 (murine 32D cells) or...