Highly refractory acute myeloid leukemia

Abstract

In this study we evaluated 103 patients suffering from acute myeloid leukemia (AML) who did not respond to induction chemotherapy and defined a sub-group of patients with highly refractory disease characterized by a persistence of more than 1 G/L blast cells in the peripheral blood between days 12 and 16 of the first induction cycle. Only seven patients (one female, six males) met these criteria. Their median age was 65 years (range 41-82 years). Four had de novo AML and three secondary AML. Cytogenetic analysis was performed in six patients: complex aberrations were detected in four patients and, unexpectedly, normal karyotypes were found in the other two. Analysis of multidrug-resistance factors revealed high co-expression of P-glycoprotein (P-gp) and lung resistance protein (LRP) in all four patients with highly refractory disease tested a finding in only 6% of patients with refractory disease and 3% of patients who achieved complete remission (CR) of disease. Furthermore, patients with highly refractory AML had substantially higher leukocyte counts than patients with refractory AML or CR, although this was not significant statistically. Overall, patients with highly refractory AML are characterized by a high incidence of complex cytogenetic aberrations and marked expression of drug transporters.

Histone deacetylase 1 induced by neddylation inhibition contributes to drug resistance in acute myelogenous leukemia

“…With developments in chemotherapy, remission rates of AML have increased dramatically (53–70%), with the curative effect of treatment dependent on the patient’s age [3]. However, most patients with AML will relapse due to multiple drug resistance with enhancing cancer cell capability to repair DNA damage and resistant to apoptosis [4, 5]. Therefore, studies of the mechanism underlying chemotherapy resistance in AML will provide the potential new therapies for prevention and treatment of AML.…”

Recent Advances in Molecular Modeling and Medicinal Chemistry Aspects of Phospho-Glycoprotein&#

“…Expression of high P-gp levels has been detected in tumor cells by various molecular and immunological probes in most tumors, such as acute myeloid leukemia [41], malignant lymphoma, ovarian cancer [42], kidney cancer, breast cancer [43], lung cancer [44], bone and colon cancers [45]. High levels of expression of the mdr1 commonly occur in human cancers derived from normal tissues, that express Pgp, such as liver, colon, kidney and pancreas [46] and these tumors are generally resistant to chemotherapy.…”