Clinical Significance of FLT-3 Internal Tandem Duplication and D835 Mutations in Acute Myeloid Leukemia Patients from West Indian Population

Introduction:The FMS-like tyrosine kinase-3 (FLT3), a member of the Platelet-derived growth factor (PDGF-R) subfamily of receptor tyrosine kinases, expressed on early hematopoietic progenitor cells play an essential role in survival and differentiation of stem cell. Majority of acute myeloid leukemia (AML) patients have mutation in this gene. Two types of frequent mutations are present in this gene. Both the types FLT3-ITD and D835 mutations play an important role in prognosis of AML patients. Methods:Total 33 patients were enrolled in the study. Blood samples were collected from the subjects, from which the DNA isolation was carried out.For FLT3-ITD mutation, PCR was performed and for D835 mutation PCR-RFLP was performed. DNA segments were amplified using Polymerase Chain Reaction (PCR). Results: FLT-3 ITD mutation was detected in 12% of patients and D835 mutation was detected in 3% of patients. The study revealed significant correlation between ITD and Tdt, while D835 negatively correlated with CD33, HLADR and Tdt. However, there was no substantial correlation of D835 with LDH value. also revealed that FLT-3 ITD significantly correlated with LDH values in AML patients. The mean value of LDH was 753.45 IU/L in ITD positive patients as compared to ITD negative patients with 338 IU/L mean LDH value, suggesting higher LDH values in ITD positive. Conclusion:These Genotypic analysis of FLT-3 mutation results from West Indian population provide important tools for understanding of AML pathogenesis and determination of appropriate therapeutic intervention. Further large number of patient data can also corroborate these significant results.

XRCC2 and XRCC3 Polymorphisms and Breast Cancer - A Case-Control Study from West India

Background:The double strand break repair pathway, comprising XRCC2 and XRCC3 has crucial role in maintenance of genomic stability and prevention of tumor initiation and progression. Therefore, sequence variants of such DNA repair genes may compromise individual's DNA repair capacity and can influence risk of developing breast cancer. Method and Results:To estimate the impending effect of XRCC2 (Arg188His) and XRCC3 (Thr241Met) polymorphisms on breast cancer, 133 breast cancer patients and 154 healthy controls were evaluated by PCR-RFLP method. In the present study, it was noted that there was no significant correlation between these polymorphisms and breast cancer risk. However, within patient group, significant association of XRCC2 variants with PR negative breast cancer was detected. Further, patients with XRCC2 variant genotypes were also at high risk of developing TNBC and Her2 enriched subtypes as compared to luminal A subtype. Significant relation was also obtained between XRCC3 variants and large sized and infiltrative breast tumors. Conclusion: These noteworthy observations demonstrate potential involvement of XRCC2 and XRCC3 polymorphisms in pathophysiology of breast cancer.