Analysis of factors that affect in vitro chemosensitivity of leukaemic stem and progenitor cells to gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukaemia

CD34+/CD38- stem cells in chronic myeloid leukemia express Siglec-3 (CD33) and are responsive to the CD33-targeting drug gemtuzumab/ozogamicin

“…19,[34][35][36] With regard to gemtuzumab/ozogamicin, it has also been reported that MDR1 is involved in the mechanism of drug-efflux, and thus resistance, in AML and CML cell lines. 37,38 Therefore, we asked ourselves whether CML LSC (CD34 + /CD38 -) express MDR1. However, in this study, we were unable to detect substantial amounts of the MDR1 antigen on the surface of CD34 + /CD38 -cells in our CML patients.…”

Leukemic stem cells: identification and clinical application

“…Treatment with Gemtuzumab ozogamicin (GO) treatment was associated with reduced relapse risk and improved overall survival in patient subgroups [49,50]. Whether GO targets CD33+ LSC, causing the reduction in relapse risk, remains unclear [50] as higher numbers of CD34+/CD38−/CD33+ cells and high CD33 expression levels decreased GO sensitivity in vitro [51]. One lesson that can be learned from GO treatment is clear: high specificity of the therapy is important.…”

Monoclonal antibody therapy directed against human acute myeloid leukemia stem cells

“…In the case of AML, the anti-CD33 monoclonal antibody conjugate gemtuzumab ozogamicin (Mylotarg) was originally given accelerated approval by the FDA for the treatment of relapsed AML in elderly patients, in whom it induced some complete remissions (Burnett and Mohite, 2006;Stasi et al, 2008). Moreover, a new report suggests that CD33 is expressed on a subset of CD34 þ CD38À LSC that can be killed by Mylotarg in vitro (Jawad et al, 2010). However, post-approval clinical trials demonstrated no benefit from the addition of Mylotarg to induction or maintenance therapy, no improvement in survival outcomes, and increased hepatic toxicity.…”