DETECTION OF FLT3 GENE INTERNAL TANDEM DUPLICATIONS AND TYROSINE KINASE DOMAIN MUTATIONS IN ACUTE MYELOID LEUKEMIA USING AUTOMATED SEQUENCING TECHNIQUE

 

Immunology, microbiology, genetics

 

Abstract.

Aim of research is to identify frequency of appearance of internal tandem duplications and point mutations of FLT3 gene in AML depending on morphological, cytogenic features and presence of alterations of TP53, NPM1, KIT, N-RAS and WT1 genes. Frequency of FLT3 gene exon 12-15 and 19-21 mutations was detected using automatic sequencing technique in AML was 14,1% and differed depending on morphological type, karyotype of leukemic blasts and also on presence of genetic abnormities in other oncogenes and tumor suppressor genes. Internal tandem duplications of FLT3 gene in AML with high frequency identify with tetranucleotide insertion of exon 12 NPM1 gene, being secondary genetic event which determines cooperation of alteration of genes expression device and cell signal pathways on molecular level. Parallel detection of genes FLT3 and KIT mutations is probably accident event because these genetic abnormalities are related to one class of molecular alterations. Cooperation of molecular alterations caused by gene FLT3 ITD and mutations of tumor suppressor genes TP53 and WT1 was not found.

 

acute myeloid leukemia, FLT3 gene, mutation's rate, sequencing

 

Authors

Vinogradov Alexander V. 

vinogradov-av@russia.ru

Ural State Medical Academy, Sverdlovsk Regional State Clinical hospital No 1, 

620028, Russia, Ekaterinburg, Repin str., 3, USMA 

 

Rezaikin Alexey V. 

alexrez@usma.ru

Ural State Medical Academy, 

620028, Russia, Ekaterinburg, Repin str., 3, USMA 

 

Sergeev Alexander G. 

sergeev@usma.ru

Ural State Medical Academy 

620028, Russia, Ekaterinburg, Repin str., 3, USMA