SHP-1 expression in chronic myeloid leukemia ( clinical significance and impact on response to imatinib treatment)

Abstract

Background SH2-containing tyrosine phosphatase (SPH-1) is a negative regulator of protein tyrosine kinases and is also a tumor suppressor that is physically and functionally linked to BCR-ABL, the hallmark for pathogenesis, diagnosis, and targeted therapy in chronic myeloid leukemia (CML). Aim This study aimed at investigating the levels of SHP-1 mRNA during chronic phase (CP), accelerated phase (AP), and blast phase (BP) CML and also assessing its impact on the response of CP-CML patients to imatinib mesylate (IM) therapy. Patients and methods The study was carried out on 77 newly diagnosed CML patients (56 CP, 13 AP, and eight BP). Ten age-matched and sex-matched volunteers free from any hematological or nonhematological malignancies served as the control group. Patients were diagnosed and classified into appropriate phases according to the WHO criteria by clinical and radiological examination, cytomorphological analysis, neutrophil alkaline phosphatase scoring, conventional cytogenetic analysis, FISH for t(9; 22) and real-time quantitative PCR analysis for BCR-ABL fusion transcripts. CP patients received IM therapy and were followed up for assessment of the response to treatment. SHP-1 mRNA levels were measured at diagnosis using real-time quantitative PCR. Results SHP-1 levels were highly significantly increased in CP-CML patients (5.8–538; median 48.1) compared with normal controls (2.6–8.3; 5.2) and patients presenting with AP (2.1–168; 13.8) or BP (1.9–173; 12.3) ( P P Conclusion SHP-1 mRNA expression is downregulated in patients with more progressive CML. Moreover, determining the SHP-1 levels at diagnosis can provide a biological predictor of the IM response in patients with CP-CML.