Studying the Impact of Presence of Alpha Acid Glycoprotein and Protein Glycoprotein in Chronic Myeloid Leukemia Patients Treated with Imatinib Mesylate in State of Qatar

• Published in: Blood 2015-12, Vol.126 (23), p.4846-4846
• Main Authors: Al-Dewik, Nader I, Jewell, Andrew, Yassin, Mohamed A., Morsi, Hisham
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V126.23.4846.4846

Background Despite the efficacy of Imatinib Mesylate (IM) in treating Chronic Myeloid Leukemia (CML), a high degree of resistance has already been noted. Alpha acid glycoprotein (AGP) may reduce drug efficacy through its ability to interact with IM and blocks it from reaching its target while Protein glycoprotein (PGP) may reduce the intracellular concentration of the drug via an active pump mechanism. In our cohort of patients with the highest rate of resistance to IM globally, we investigated if the level of AGP and PGP could be correlated with CML resistance/response to IM? and if so, could they be employed as biological markers for CML resistance to treatment? Methods To answer these questions, the 26 CML patients who were enrolled into our previous study between November 2006 and December 2011 were investigated for AGP and PGP levels at diagnosis and during treatment. Serum samples were analyzed to determine AGP level via an Immunoturbidimetric assay and up-regulation of PGP level was determined via Flow cytometry analysis of Peripheral Blood (PB) and Bone Marrow (BM) samples. Results A total of 100 serum, 40 BM & 100 PB samples were collected from the 26 CML patients (22 CP & 4 AP) treated at the National Center for Cancer Care and Research (NCCCR) in Qatar. Samples from 10 healthy volunteers were collected as a control. AGP results At Diagnosis 11/22 CP patients had elevated AGP (mean 1.5 ±0.11 g/l) while 3/4 AP patients had elevated AGP (mean 1.8 ±0.3 g/l). During follow-up The mean AGP values among the 14/26 patients who failed IM treatment were (1.05 ±0.09 g/l) while the values for the 12 patients who responded to the treatment were not significantly different (1.1 ±0.06 g/l) (p =) > 0.05. The 10/14 resistant patients who were previously reported to have mutations/Additional Chromosomal Abnormalities (ACAs) as underlying mechanisms of resistance, showed a mean AGP level of 1.06 (±0. 09) while the 4/14 patients with no mutations/ACAs showed no significant difference (AGP leve1.04 ±0.08) (p =) > 0.05. The mean value of the 10 healthy individuals who were enrolled as a control group was 0.71 ±0.04 g/l. The mean AGP levels were 1.2 (±0.12), 1.61 (±0.38), 1.05 (±0.09), 1.1 (±0.06), and 0.71(±0.04) g/l for 22/26 CP, 4/26 AP, 14/26 failed treatment, 12/26 optimal responders and controls respectively and the differences between patients groups and the control group on other hand were significant (p) 0.001, 0.03, 0.003, and 0.005 respectively. There was n