Frequency of FLT3 Internal Tandem Duplications in Adult Syrian Patients with Acute Myeloid Leukemia and Normal Karyotype

Alarbeed, Ismael F.; Wafa, Abdulsamad; Moassass, Faten; Al‐Halabi, Bassel; Al‐Achkar, Walid; Aboukhamis, Imad

doi:10.31557/apjcp.2021.22.10.3245

Cited by 3 publications

(2 citation statements)

References 45 publications

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“…In FLT3-positive AML patients, mutations have been observed in the FLT3 gene on chromosome 13. The most prevalent of the FLT3 mutations is the internal tandem duplication (ITD) which is found in 15–30% of the AML patients [ 44 , 46 , 47 , 48 ]. The FLT3-ITD is an in-frame duplication in the juxtamembrane domain of the intracellular region of the FLT3 receptor ( Figure 2 ).…”

Section: The Choice Of Flt3 As Target For Car T-cell Therapymentioning

confidence: 99%

“…The second most prevalent FLT3 mutation is in the tyrosine kinase domain (TKD), which 5–10% of AML patients harbor [ 48 , 51 ]. The FLT3-ITD mutations are associated with reduced overall survival and are predictors of poor prognosis [ 43 , 46 , 51 , 52 ]. Thiede et al found that the risk of relapse was 1.6 with a median ratio (ITD/WT genotype) above 0.78 and poor overall survival, which is consistent with Whitman et al that found an overall survival rate of 74% for the FLT3 WT/WT genotype compared to 13% ( p = 0.008) for the FLT ITD/-genotype [ 48 , 53 ].…”

Section: The Choice Of Flt3 As Target For Car T-cell Therapymentioning

confidence: 99%

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Recent Advances in the Development of Anti-FLT3 CAR T-Cell Therapies for Treatment of AML

2022

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Following the success of the anti-CD19 chimeric antigen receptor (CAR) T-cell therapies against B-cell malignancies, the CAR T-cell approach is being developed towards other malignancies like acute myeloid leukemia (AML). Treatment options for relapsed AML patients are limited, and the upregulation of the FMS-like tyrosine kinase 3 (FLT3) in malignant T-cells is currently not only being investigated as a prognostic factor, but also as a target for new treatment options. In this review, we provide an overview and discuss different approaches of current anti-FLT3 CAR T-cells under development. In general, these therapies are effective both in vitro and in vivo, however the safety profile still needs to be further investigated. The first clinical trials have been initiated, and the community now awaits clinical evaluation of the approach of targeting FLT3 with CAR T-cells.

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Section: The Choice Of Flt3 As Target For Car T-cell Therapymentioning

confidence: 99%

Section: The Choice Of Flt3 As Target For Car T-cell Therapymentioning

confidence: 99%

Recent Advances in the Development of Anti-FLT3 CAR T-Cell Therapies for Treatment of AML

2022

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Plasma cell-free DNA in patients with acute promyelocytic leukaemia treated with arsenic trioxide

Fujihara,

Nishimoto,

Takeshita

2023

Ann Clin Biochem

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Background Cell-free DNA (cfDNA) is free DNA found in circulating blood that originates from apoptosis or necrosis, and elevated cfDNA concentrations have been reported in cancers and other diseases. Methods In this study, the concentrations and fragment distributions of plasma cfDNA were preliminary investigated in elderly ( n = 1) and paediatric ( n = 1) patients with acute promyelocytic leukaemia (APL) treated with arsenic trioxide (ATO). Results A slight increase in cfDNA concentrations was observed in the APL patients compared with healthy controls. The change in plasma cfDNA concentrations corresponded to the change in plasma arsenic concentrations during ATO treatment. The fragment distribution pattern did not differ before and during treatment. Three ladder fragments were observed in part of the cfDNA in the second consolidation therapy in an elderly APL patient and the first consolidation therapy of a paediatric APL patient, while two fragments were observed in all other treatment periods. Moreover, APL-related gene mutations were successfully genotyped from plasma cfDNA by using polymerase chain reaction-based methods and these results are consistent with those from leukocytes. Conclusion This study is the first to report the concentrations and fragment patterns of cfDNA from APL patients treated with ATO. The results suggested that plasma cfDNA concentration in APL patients increased with ATO treatment and that cfDNA is released mainly via neutrophil extracellular traps (and/or necrosis) in addition to apoptosis. To confirm whether cfDNA concentrations and fragment patterns can be used as a biomarker for APL treated with ATO, further accumulative data are needed.

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FLT3 Mutations in Acute Myeloid Leukemia: Unraveling the Molecular Mechanisms and Implications for Targeted Therapies

Jalte,

Abbassi,

El Mouhi

et al. 2023

Cureus

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Acute myeloid leukemia (AML) is a heterogeneous and aggressive form of blood cancer characterized by the uncontrolled proliferation of myeloid precursor cells in the bone marrow. It affects individuals of all ages, with incidence increasing notably in those over 65 years old. Despite advancements in treatment, overall survival rates remain unsatisfactory, underscoring the need for a deeper understanding of the disease. Among the various genetic alterations implicated in AML pathogenesis, mutations in the FLT3 (Fms-like tyrosine kinase 3) gene have emerged as significant contributors to leukemogenesis. The FLT3 gene encodes a type III receptor tyrosine kinase crucial in regulating normal hematopoiesis. Approximately one-third of AML patients carry FLT3 mutations, making it one of the most frequently mutated genes in the disease. FLT3 mutations can be classified into internal tandem duplications (ITDs) and point mutations in the tyrosine kinase domain (TKD). FLT3 mutations are associated with adverse clinical features and are independent prognostic factors for poor overall survival and decreased remission rates in AML patients. Understanding the molecular mechanisms underlying FLT3 mutations in AML is critical for improving risk stratification, prognosis assessment, and the development of targeted therapies. By reviewing the current literature, this study aims to elucidate the functional consequences of FLT3 mutations in AML pathogenesis, explore the interaction of FLT3 signaling with other oncogenic pathways, and assess the prognostic significance of FLT3 mutations in clinical practice, providing information that can guide future research directions and facilitate the development of more effective therapeutic strategies.

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Frequency of FLT3 Internal Tandem Duplications in Adult Syrian Patients with Acute Myeloid Leukemia and Normal Karyotype

Cited by 3 publications

References 45 publications

Recent Advances in the Development of Anti-FLT3 CAR T-Cell Therapies for Treatment of AML

Recent Advances in the Development of Anti-FLT3 CAR T-Cell Therapies for Treatment of AML

Plasma cell-free DNA in patients with acute promyelocytic leukaemia treated with arsenic trioxide

FLT3 Mutations in Acute Myeloid Leukemia: Unraveling the Molecular Mechanisms and Implications for Targeted Therapies

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