Mona Padidaran - Biotechnology Research Center, International Campus, Shahid SadoughiUniversity of Medical Sciences, Yazd, Iran

Introduction:AML (acute myeloid leukemia) is a heterogeneousdisease with many mutations of different genes affectingpatients' prognoses. Among which is the FLT۳ (Fms-relatedreceptor tyrosine kinase ۳) playing an important role in the selfrenewaland differentiation of hematopoietic stem and progenitorcells.Methods:“AML”, “prognostic”, and “FLT۳” keywords weresearched through the PubMed database. The quest was Confinedto the last ۵ years of clinical trials. Ultimately, the morerelevant papers to the main idea were chosen.Results: Though, FLT۳ mutations, ITD (internal tandem duplication)but not TKD (Tyrosine Kinase Domain) mutationshave a higher relapse rate and inferior OS (Overall Survival).Still, the prognostic impact of FLT۳ ITD is context-dependent.Even the IS (insertion site) of ITD has an effect on prognosis.A trial illustrated that mutations within NPM۱, DNM۳A,and WT۱ were the three most frequent ones co-occurring withFLT۳ mutation. The poorest prognostic impact was found forWT۱. And NPM۱ conferred the highest favorable prognosis toFLT۳- mutated patients. WT۱:NPM۱ showed A striking effectwith NPM۱ abrogating the negative effect of WT۱ mutation,and midostaurin exerted a significant beneficial effect in WT۱-mutated patients. By evaluating OS and Cumulative Incidenceof Relapse, ITD insertion in TKD۱ site was recognized as anunfavorable prognostic factor for AML patients that could notbe overcome by midostaurin. And, midostaurin exerted a significantbenefit only for patients with ITDs inserted in JMD (juxtamembranedomain). Applying oral azacitidine (Oral-AZA) inpatients with AML in CR۱, significantly improved survival inpatients with adverse (FLT۳mut/MRD+) prognostic AML features.Adding sorafenib to the IC regimen showed improvementin the outcome of FLT۳ ITD mutated patients irrespective ofallele burden. In relapsed or refractory FLT۳-mutated AML patients,two drugs were examined; giltertinib, and quizartinib.Both gave a better survival benefit in comparison with salvagechemotherapy.Conclusion: Based on this review, we can conclude that theFLT۳ mutations prognosis effect is influenced by a mutationalbackground and that, ISs in FLT۳-ITD have different impacts.Besides, this review highlights the beneficial effect of kinaseinhibitors, as well as azacitidine (a hypomethylating agent) onFLT۳-mutated AML patients’ prognosis

AML, FLT۳, Prognosis, Kinase inhibitors, Insertionsite, mutational background