Application of HRM Analysis in Detection of PDGFRA Exon 10 Polymorphism in CML Patients with Imatinib Resistance

@#Introduction: Imatinib mesylate has been widely used as a standard treatment for chronic myeloid leukemia (CML). It acts as a selective competitive inhibitor of the BCR-ABL tyrosine kinase. Despite the excellent efficacy on CML treatment, some patients developed resistance to the treatment. Mutation in the PDGFRA may be one of the factors involved in the mechanism of resistance that affects the response to imatinib. The mutational status of PDGFRA is highly relevant for prognosis and treatment prediction in CML patients. Thus, this study is intended to establish and validate a High Resolution Melting (HRM) analysis for PDGFRA exon 10 c.1432 T>C polymorphism in CML patients. Methods: High resolution melting (HRM) analysis was used to identify the c.1432 T > C polymorphism in PDGFRA exon 10 (n =86; response = 43; resistance = 43). The results from HRM analysis were compared and validated with Sanger sequencing. The association between the polymorphism and treatment response was assessed by statistical analysis using binomial logistic regression analysis. Results: HRM analyses showed two different melt curves. One curve followed the shape of the reference, homozygous wild type (TT) and the other curve showed a different melting profile than the reference with the TC genotype (heterozygous variant). The results revealed that heterozygous variant (TC) genotype showed a high risk of acquiring resistance with an OR of 3.795; 95% CI: 1.502-9.591, with a statistically significant association, p = 0.005. HRM analysis also showed 100% sensitivity and specificity in the detection of PDGFRA exon 10. Conclusion: The HRM analysis of PDGFRA exon 10 c.1432 T>C was successfully established. The exon 10 c.1432 T>C polymorphism shows a higher risk for the development of resistance toward imatinib treatment.

Autologous peripheral blood stem cell transplantation among lymphoproliferative disease patients: factors influencing engraftment

Objectives: Autologous peripheral blood stem cells transplantation [APBSCT] is a therapeutic option which can be used in various hematological, neoplastic disorders including lymphoproliferative disease [LPD]. Differences in patient populations and treatment modalities in different transplant centers mean it is important to improve the knowledge of the different factors affecting engraftment after APBSCT for the success of this procedure. We sought to determine the factors influencing neutrophil and platelet engraftment after APBSCT in patients with LPD

Methods: We conducted a retrospective review of 70 patients with LPD [35 with lymphoma and 35 with multiple myeloma] who had undergone APBSCT between January 2008 and December 2016. Data obtained included disease type, treatment, and stem cell characteristics. Kaplan-Meier analysis was performed for probabilities of neutrophil and platelet engraftment occurred and was compared by the log-rank test. The multivariate Cox proportional hazards regression model was used for the analysis of potential independent factors influencing engraftment. A p-value < 0.050 was considered statistically significant

Results: Most patients were ethnic Malay, the median age at transplantation was 49.5 years. Neutrophil and platelet engraftment occurred in a median time of 18 [range 4–65] and 17 [range 6–66] days, respectively. The majority of patients showed engraftment with 65 [92.9%] and 63 [90.0%] showing neutrophil and platelet engraftment, respectively. We observed significant differences between neutrophil engraftment and patient's weight [< 60/>/= 60 kg], stage of disease at diagnosis, number of previous chemotherapy cycles [< 8/>/= 8], and pre-transplant radiotherapy. While for platelet engraftment, we found significant differences with gender, patient's weight [< 60/>/= 60 kg], pre-transplant radiotherapy, and CD34+ dosage [< 5.0/>/= 5.0 × 106/kg and < 7.0/>/= 7.0 × 106/kg]. The stage of disease at diagnosis [p = 0.012] and pre-transplant radiotherapy [p = 0.025] were found to be independent factors for neutrophil engraftment whereas patient's weight [< 60/>/= 60 kg, p = 0.017], age at transplantation [< 50/>/= 50 years, p = 0.038], and CD34+ dosage [< 7.0/>/= 7.0 × 106/kg, p = 0.002] were found to be independent factors for platelet engraftment

Conclusions: Patients with LPD who presented at an early stage and with no history of radiotherapy had faster neutrophil engraftment after APBSCT, while a younger age at transplantation with a higher dose of CD34+ cells may predict faster platelet engraftment. However, additional studies are necessary for better understanding of engraftment kinetics to improve the success of APBSCT

Commemorating the 40-Year Journey of the School of Medical Sciences, Universiti Sains Malaysia

@#The School of Medical Sciences of Universiti Sains Malaysia (USM) is the launching pad for this journal. From the school’s humble beginning at the USM Main Campus in Pulau Pinang, Malaysia, it has grown in stature at its current location in the USM Health Campus, Kubang Kerian, Kelantan, Malaysia. Commemorating its 40th anniversary, this editorial aims to recollect, although not exhaustively, the wealth of returns for the USM, as well as for the nation, which the school has managed to deliver in that period. Resolute to its vision and mission, this article highlights the outstanding accomplishments in various core aspects of the school’s academic, research and professional growth as we continually strive to train globally competitive and compassionate medical graduates, medical specialists and scientists, skilled to serve nation’s needs and broader markets worldwide. Currently guided by the Malaysian Higher Education Blueprint (2015–2025), the school shall remain ingenious in its duties in the many more years to come, as we head for a world-class trajectory.

Potential use of cord blood for Hb E hemoglobinopathy screening programme using capillary electrophoresis

Background: Thalassemia and hemoglobinopathies are inherited red blood cell disorders found worldwide. Hemoglobin (Hb) E disorder is one of the hemoglobinopathies known to have the high prevalence in South East Asia. Most of transfusion-dependent thalassemias were genotypically compound heterozygous Hb E/ β-thalassemia. In Malaysia, the national screening program for thalassemia was implemented for early pregnancy or secondary school girls; however many participants do not turn-up and missed the screening test. Screening for thalassemia using samples from cord blood is an alternative choice as it is a readily available source of blood and hence early detection of the disease. The purpose of this study was to determine the potential use of cord blood for the screening of HbE hemoglobinopathy by using capillary electrophoresis (CE). Methods: Cord blood samples were collected from 300 newborns of healthy mothers. Hematological parameters were determined and hemoglobin quantitation for all cord blood samples were performed using capillary electrophoresis system (CES) and high performance liquid chromatography (HPLC). Results: Majority of cord blood samples (63%) revealed Hb AF followed by Hb AFA2 (20%). Hb AFE was detected in 10.7% with the mean value of Hb E ranging from 2.3%-11.1%. Conclusion: Hemoglobin E was detected in cord blood using capillary electrophoresis system. It can be recommended in areas where Hb E/β is prevalent. Implementation of a screening strategy using CE on cord blood sampling will identify the disease early. With regular follow-up on these patients, the status of their disease can be determined earlier and appropriate management implemented.