Onkológia 3/2018
FLT3mutácie u pacienta s AML: incidencia, možnosti diagnostiky a vplyv na manažment liečby
FLT3mutations in AML: incidence, diagnostics options and its impact on treatment management Purpose: Acute myeloid leukemia (AML) is clonal hematologic malignancy occurring mainly in elderly population, resulting into clonal expansion of myeloid blasts in the peripheral blood, bone marrow, circulation and infiltrated into other tissues. Formally a life-threatening disease is now curable in 35 – 40 % of younger patients. In newly diagnosed AML cases there have been noticed an interesting mutation in the tyrosine kinase Flt3 (FMS-like tyrosine kinase 3) (published incidence about 30 %) that negatively affect the survival. Patients’ cohort and methods: Retrospectively we have analyzed data collected by two genetic laboratories covering patients from whole Slovakia over past two year period. In 364 patients newly diagnosed AML, we have tested FLT3mutations: FLT3-ITD, FLT3-TKD codon D835 (189 pts in 2016 and 175 pts in 2017). Results: Altogether, we have found 62 pts barring FLT3mutation. Out of them 44 pts were FLT3-ITD and 18 FLT3-TKD codon D835 positive resp. In 2016 there have been identified 33 of those cases and the remaining 29 cases were diagnosed in 2017. By analyzing our patients’ cohort we have found that the yearly incidence in all newly diagnosed AML cases is about 17% (17.4% in 2016 and 16.5% in 2017 resp.). In our case, the incidence was lower comparing to already published data that can be explained by the assessment test sensitivity varying from country to country, size of an examined patients’ cohort, genetic variability in given population, age of patients and environmental factors. Nowadays, we also perform the gene allelic burden (mutant/wild type ratio) assessment. Conclusion: Genetic changes found in AML can be used as possible therapeutic targets. Understanding of the disease biology and new drug development is vital for radical prognosis improvement. AML treatment incorporates new targeted drugs such as midostaurin, gemtuzumab ozogamicine in the 1st line and enasidenib in relaps/refractory AML that changed treatment results in predefined group of patients. New liposomal form of daunorubicine/cytarabine is approved, which can change the standard treatment in elderly population. High frequency of FLT3mutations and their prognostic relevance in adult and pediatric AML patients represent a suitable therapeutic target.
Keywords: Acute myeloid leukemia, FLT3mutation, incidence, FLT3-ITD, FLT3-D835
