Acute Myeloid Leukaemia (AML) is one of the common forms of haematological malignancy in adults. We analysed the prevalence and clinical significance of FMS-like tyrosine kinase 3 (FLT3) and Nucleophosmin 1 (NPM1) mutations in AML patients of North East India. Co-prevalence and clinical significance of three recurrent chromosomal translocations namely t(15; 17), t(8; 21), t(16; 16) and expression of epidermal growth factor receptor (EGFR), flow markers were also documented and co-related with disease progress. We analysed bone marrow aspirates or peripheral blood samples from 165 newly diagnosed AML patients. All clinical samples were analysed by Real Time PCR and DNA sequencing based assays. NPM1 was the most frequently detected mutation in the study population (46/165 = 27.90%, 95% CI 20.75-35.05). FLT3 mutations were detected in 27/165 (16.40%, 95% CI 10.45-22.35) patients with internal tandem duplication (FLT3-ITD) in 24/165 (14.60%, 95% CI 8.91-20.29) and FLT3-D835 in 3/165 (1.80%, 95% CI 0-4.13) patients. NPM1 mutations were associated with a higher complete remission rate and longer overall survival ( < 0.01) compared to FLT3-ITD whereas FLT3-ITD showed adverse impact with poor survival rate ( < 0.01), leukocytosis ( < 0.01) and a packed bone marrow. EGFR expression was more in patients with NPM1 mutation compared to FLT3 mutation ( = 0.09). Patients with FLT3 and NPM1 mutations uniformly expressed CD13 and CD33 whereas CD34 was associated with poor prognosis ( ≤ 0.01) in patients with NPM1 mutation. FLT3-ITD was associated with inferior overall survival. However the clinical significance of FLT3-D835 was not clear due to small number of samples. NPM1 mutation showed better prognosis with increased response to treatment in the absence of FLT3-ITD.

DNMT3A R882 mutation plays an important role in CN-AML patients' prognosis and clinical outcomes in the presence and absence of NPM1 and FLT3 mutations.

Objective/Background: Acute myeloid leukemia (AML) is one of the common forms of hematological malignancy and acute promyelocytic leukemia (APL) is a unique subtype of AML conferring favorable prognosis. We aimed to determine the prevalence and prognostic impact of Fms-like tyrosine kinase 3 (FLT3), nucleophosmin 1 (NPM1) mutation, epidermal growth factor receptor (EGFR), and flow marker’s expression in patients with APL. Methods: In the present study, 165 de novo APL patients were molecularly characterized for promyelocytic leukemia (PML) breakpoint and additional genetic alterations. Reverse transcriptase polymerase chain reaction (PCR) and realtime PCR assays were used to detect genetic alterations. Results: PML/RARa was detected in 29/165 (17.5%) samples with breakpoint cluster region 1 (bcr1) in 17/29 (58.5%) and bcr3 in 12/29 (41.5%) samples. The prevalence of FLT3-ITD, NPM1, and EGFR were detected in 5/29 (17.5%), 11/29 (38%), and 5/29 (17.5%) patients, respectively. Patients expressing bcr-3 hybrid transcript had lower overall survival compared with bcr1 (p = .254). White blood cell (WBC) count was significantly higher in bcr3 in comparison with bcr1 patients (p = .002). Patients with positive EGFR expression (p = .042) and higher WBC (p = .002) were significantly associated with poor survival (p < .05). Conclusions: We documented the higher prevalence of bcr1 and confirmed that the association of FLT3-ITD significantly reduced the chances of survival in APL. The mortality rate of bcr3 was comparatively higher than that of bcr1. Higher WBC count and EGFR expression were significantly associated with poor survival.

Aims:To investigate the association between Vitamin D receptor gene polymorphisms (BsmI, TaqI and FokI) and type 2 diabetes mellitus in patients in north eastern India.Settings and Design:This was a case control study with 40 cases of type 2 diabetes and 20 controls.Materials and Methods:Genomic DNA was extracted from blood and genotyped for the single nucleotide polymorphism (SNPs) of BsmI [rs1544410], TaqI [rs731236] and FokI [rs2228570] by polymerase chain reaction and gene sequencing. Genotype distribution and allelic frequencies were compared between patients and controls. Data was expressed as mean ±standard deviation. Chi square test and t test were used to compare groups. Statistical analysis was done using SAS version 9.3 software. P value of <0.05 was considered significant.Results:Body weight and BMI were significantly associated with VDR polymorphisms BsmI and TaqI while BsmI was significantly associated with HbA1C. Vitamin D deficiency was significantly greater in cases than controls. The frequency of the heterozygous genotype of the BsmI polymorphism was significantly greater in type 2 diabetics than in controls.Conclusions:Vitamin D receptor polymorphisms are associated with type 2 diabetes in our population and require larger scale studies to be considered as possible risk factors or type 2 diabetes mellitus.