BackgroundDespite 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?MethodsTo 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.ResultsA 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 resultsAt Diagnosis11/22 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-upThe 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 no a significant difference or correlation between AGP levels amongst the different groups of patients and there was no significant correlation between AGP and other biomarkers such as Platelets (PLTs), White Blood Cells (WBCs), Absolute Basophils (Abs. Baso) and Lactate Dehydrogenase (LDH) of CML patients in the responders group.However, the group who failed treatment showed a strong correlation between elevated AGP and LDH (p = 0.0001), WBCs (P =0.002) and Abs. Baso (p=0.03)PGP resultsOn the other hand, the mean PGP level was 1.25 (±0.06), 1.17 (±0.02), 1.21 (±0.03), 1.2 (±0.04) for AP, CP, responders and resistant patients respectively. Flow cytometric analysis showed no significant difference in the fluorescence intensities of the blast cells incubated with CD 243 and the blast cells incubated with isotypic control among the different groups of patients.Discussion and ConclusionWith a significant difference in AGP levels between patients and controls in our cohort of CML cases, combining AGP with others markers showed significant correlations during different disease stages that may be employed as a warning sign for resistance of CML to Tyrosine Kinase Inhibitors (TKIs).PGP expression, on the other hand did not differ in patients presenting in chronic phase or accelerated phase and showed no specific pattern for those who resist or respond to IM treatment.However, neither AGP nor PGP could be employed as an independent marker for disease progression as the noticed resistance in our CML patients could not be correlated to AGP or PGP levels and regardless of response or resistance to treatment, there was no significant pattern of AGP or PGP expression. DisclosuresAl-Dewik:Qatar National Research Fund (QNRF): Other: sponsorship.