FLT3 (Phospho-Tyr969) ELISA Kit

INTRODUCTION Acute myeloid leukemia (AML) is characterized by multiple acquired genetic events, chromosomal abnormalities such as copy number aberrations (CNAs), disease progression, and low survival rates. OBJECTIVES We assessed the utility of a multiplex ligation-dependent probe amplification (MLPA) assay in AML as well as correlations of CNAs with various biological and clinical features of patients with AML, including somatic mutations in the FLT3, NPM1, and DNMT3A genes and survival. PATIENTS AND METHODS The study included 283 patients with AML. The MLPA was used for investigation of CNAs. The status of somatic mutations was analyzed in all cases. RESULTS The presence of CNAs was associated with the adverse (high) risk category according to the European LeukemiaNet (ELN) classification (P-FDR < 0.0001). The significant predictors of mortality were age of 65 years or older (hazard ratio [HR], 2.30; 95% CI, 1.71-3.09), ELN high-risk category (HR, 1.71; 95% CI, 1.15-2.56), and the Eastern Cooperative Oncologic Group Scale (ECOG) performance status grade of 3 or higher (HR, 2.43; 95% CI, 1.80-3.30), but not the presence of CNA. An interaction between CNAs and the ECOG performance status was shown (HR interaction, 2.24; 95% CI, 1.09-4.57, P = 0.02). The presence of CNAs was positively correlated with the risk of death in patients with an ECOG grade of 3 or higher (HR, 2.02; 95% CI, 1.30-3.12), while for patients with the performance status of 2 or lower, the presence of CNAs was a protective factor against the risk of death. CONCLUSIONS The presence of CNAs may modify the effect of the ECOG performance status on survival. Independent predictors of mortality in patients with AML include age, ELN adverse risk category, and the ECOG grade of at least 3.

Certain subtypes of acute myeloid leukemia occur as a result of the cooperation of several events these are, the formation of fusion genes as a result of chromosomal rearrangements, which leads to the disruption of cell differentiation, and the emergence of mutations that enhance cellular proliferation by activating intracellular signaling pathways. High-throughput sequencing methods reveal characteristic mutation spectra in leukemia associated with different chromosomal disorders. However, the role of mutation events in malignant cell transformation processes remains obscure. We searched for driver mutation events in leukemic cells containing the chimericCBFB-MYH11gene, which results from inversion of chromosome 16. Using target enrichment, the coding regions of 84 genes in genomes of 12 children with acute myeloid leukemia with inv(16) were investigated. Somatic mutations have been found in the genes of the proteins of intracellular signaling cascades mediated by receptor tyrosine kinases, such asKIT(41%),NRAS(25%),KRAS(17%), andFLT3(8.3%). Comparative analysis of samples at the time of diagnosis and during remission was used to assess the role of mutations in the pathogenesis of the disease. Previously undescribed mutations in theKDM6A,NOTCH1, andIDH1genes, which may be involved in leukemogenesis processes have been identified.