Study of PTCH1 Gene as a Prognostic Marker to Predict Imatinib Response in CML Patients: a Single Egyptian Center Experience

Abstract

Background: Chronic myeloid leukemia (CML) is a myeloproliferative illness marked by a reciprocal translocation between chromosomes 9 and 22 [t (9;22) (q34; q11)], forming the Philadelphia chromosome and bringing together the Breakpoint Cluster Region (BCR) and Abelson (ABL1) genes. The protein expressed by this fusion gene is a dysregulated tyrosine kinase that causes alterations in cell proliferation, DNA repair, differentiation, and cell cycle by phosphorylating many downstream proteins. Objectives: To assess PTCH1 gene expression and response of adult patients with chronic myeloid leukemia to imatinib treatment. Patients and Methods: This is a prospective case-control study that included 55 subjects; 45 patients with chronic phase chronic myeloid leukemia and 10 healthy age and sex-matched controls. The control group presented from the same geographic origin of the patients in the study group. The study was done between June 2015 and July 2017 at the hematology clinic, Ain Shams University Hospital. Results: PTCH1 gene was more in cases than control with a statistical significance (P-value=0.024). On following up our cases after 6 months treatment with imatinib, patients with desired response to imatinib treatment had a mean of PTCH1 gene expression of 2.41, compared to 3.58 in patients who did not achieve desired response with a statistical significance with p-value = 0.017. Incidence of imatinib failure after 6 months of treatment in patients with high PTCH1 expression is 27.8 % while in those with low expression is 44.4 %. Conclusion:The study demonstrates that level of PTCH 1 did not affect imatinib response. Therefore, PTCH1 is not a valid biomarker for imatinib resistance in CML patients.

Patched Homolog Gene (PTCHI) As a Reliable Marker for Predicting Imatinib Response in Chronic Phase Chronic Myeloid Leukemia Patients in Correlation with Early Response to First Line of Treatment Imatinib

“…The median initial level of PTCH1 was 6000 ng/L (range: 2500-10000) while its median after treatment was 20 ng/L (rang: 10-30) so we found that there was high expression of initial PTCH1 protein level. Our finding agrees with Moussa et al [8] who conducted prospective case-control study that included 55 subjects: 45 patients with CP-CML and 10 healthy age and sex-matched controls. PTCH1 mRNA level was detected by real time RT-PCR and found that PTCH1 gene was more expressed in CML cases than in control (P=0.024).…”

“…Patients who attained deep molecular response had lower level of PTCH1 protein initially and after 6 months than patients with major and early molecular response. Our results agree with Moussa et al [8] who reported that patients with good response to imatinib had lower PTCH1 gene expression than patients who did not achieve good response to imatinib (P=0.017). Also, Abd Elrhman et al [10] to determine if the PTCH1 gene mutation exists or not, 50 CML patients who had recently diagnosed, and 10 healthy controls were tested.…”