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2021, Number 3

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Rev Hematol Mex 2021; 22 (3)

FMS-like tyrosine kinase 3 (FLT3) gene: From the biogenesis to the medical practice

Garrote-SH

Language: Spanish
References: 84
Page: 162-174
PDF size: 285.53 Kb.


ABSTRACT

The FMS-like tyrosine kinase 3 (FLT3) gene encodes an essential receptor in the development, proliferation and survival of hematopoietic cells. This article describes the biological characteristics of the gene, the normal and pathological functioning of the protein, and the main mutations of interest in medical practice. FLT3 is located on chromosome 13 and is made up of 24 exons. Protein synthesis and subsequent activation depend on different cellular processes and the FLT3 ligand. Among the most important alterations of the gene, the internal tandem duplication in the coding region of the juxtamembrane domain (FLT3-ITD) and point mutations in the tyrosine kinase domain (FLT3-TKD). These mutations are of special interest for making therapeutic decisions in acute myeloid leukemia (AML). The FLT3-ITD alteration is described in up to 25% of patients with acute myeloid leukemia and is an independent predictor of poor prognosis and increased risk of relapse. The allelic ratio (AR) FLT3-ITD, which reflects the leukemic burden, has a significant role, where the AR ‹ 0.5 or ≥ 0.5 defines prognostic categories. Regarding therapeutic regimens, clinical trials with inhibitors of the FLT3 protein, targeting both FLT3-ITD and FLT3-TKD mutations, have opened a door to precision medicine in acute myeloid leukemia, however, there are still obstacles to overcome such as toxicity, specificity and resistance in the patient.


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