Редактирование: FLT3

Receptor-type tyrosine-protein kinase FLT3 precursor (EC 2.7.10.1) (FL cytokine receptor) (Fetal liver kinase-2) (FLK-2) (Fms-like tyrosine kinase 3) (FLT-3) (Stem cell tyrosine kinase 1) (STK-1) (CD135 antigen) [CD135] [FLK2] [STK1]

==Publications==

{{medline-entry
|title=Sequential acquisition of mutations in myelodysplastic syndromes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28978821
|abstract=Recent progress in next-generation sequencing technologies allows us to discover frequent mutations throughout the coding regions of myelodysplastic syndromes (MDS), potentially providing us with virtually a complete spectrum of driver mutations in this disease. As shown by many study groups these days, such driver mutations are acquired in a gene-specific fashion. For instance, [[DDX41]] mutations are observed in germline cells long before MDS presentation. In blood samples from healthy elderly individuals, somatic [[DNMT3A]] and [[TET2]] mutations are detected as age-related clonal hematopoiesis and are believed to be a risk factor for hematological neoplasms. In MDS, mutations of genes such as [[NRAS]] and [[FLT3]], designated as Type-1 genes, may be significantly associated with leukemic evolution. Another type (Type-2) of genes, including [[RUNX1]] and [[GATA2]], are related to progression from low-risk to high-risk MDS. Overall, various driver mutations are sequentially acquired in MDS, at a specific time, in either germline cells, normal hematopoietic cells, or clonal MDS cells.
|mesh-terms=* Aging
* DEAD-box RNA Helicases
* Genome, Human
* Humans
* Mutation
* Myelodysplastic Syndromes
* Prognosis
|keywords=* Germline mutations
* Myelodysplastic syndromes
* Secondary acute myeloid leukemia
* Somatic mutations
|full-text-url=https://sci-hub.do/10.11406/rinketsu.58.1828
}}
{{medline-entry
|title=RAS mutations contribute to evolution of chronic myelomonocytic leukemia to the proliferative variant.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20371679
|abstract=The biological and clinical heterogeneity of chronic myelomonocytic leukemia features renders its classification difficult. Moreover, because of the limited knowledge of the mechanisms involved in malignant evolution, chronic myelomonocytic leukemia remains a diagnostic and therapeutic challenge and a poor prognosis disease. We aimed to verify the biological and clinical significance of the discrimination, based on the leukocyte count, between myelodysplastic chronic myelomonocytic leukemia (MD-CMML) and myeloproliferative chronic myelomonocytic leukemia (MP-CMML). Peripheral blood samples from 22 patients classified as MD-CMML and 18 as MP-CMML were collected at different time points during disease course, and patients' clinical characteristics were examined. RAS mutational screening was done by sequencing and, for each substitution identified, a highly selective allele-specific PCR was set up to screen all specimens. MP-CMML patients showed a significantly poorer survival (P = 0.003) and a higher frequency of RAS mutations (P = 0.033) by sequencing compared with MD-CMML. Overall, five MD-CMML patients progressed to myeloproliferative disease: in two, allele-specific PCR unveiled low levels of the RAS mutations predominating in the myeloproliferative phase at the time of myelodysplastic disease, documenting for the first time the expansion of a RAS mutated clone in concomitance with chronic myelomonocytic leukemia evolution. Moreover, one of the progressed patients harbored the [[FLT3]]-ITD and two MP-CMML patients presented with the [[JAK2]] V617F substitution. All these lesions were mutually exclusive. Our results strongly suggest RAS mutations to function as a secondary event that contributes to development of the chronic myelomonocytic leukemia variant with the poorer prognosis (MP-CMML) and therefore advise their detection to be implemented in chronic myelomonocytic leukemia diagnostics and monitoring.
|mesh-terms=* Aged
* Aged, 80 and over
* Animals
* Colony-Forming Units Assay
* Disease Progression
* Evolution, Molecular
* Female
* Genes, ras
* Guanosine Triphosphate
* Humans
* Janus Kinase 2
* Leukemia, Myelomonocytic, Chronic
* Life Expectancy
* Male
* Mice
* Middle Aged
* Mutation
* Myelodysplastic Syndromes
* Myeloproliferative Disorders
* NIH 3T3 Cells
* Prognosis
* Proto-Oncogene Proteins
* Proto-Oncogene Proteins p21(ras)
* Survival Rate
* fms-Like Tyrosine Kinase 3
* ras Proteins

|full-text-url=https://sci-hub.do/10.1158/1078-0432.CCR-09-2112
}}
{{medline-entry
|title=The relationship of patient age to the pathobiology of the clonal myeloid diseases.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/15112149
|abstract=The incidence of the major clonal myeloid diseases, clonal cytopenias, acute, subacute (oligoblastic), and chronic myelogenous leukemia, polycythemia vera, thrombocythemia, and idiopathic myelofibrosis increases in a log-linear manner from young adulthood through advanced age. In older patients, diseases requiring cytotoxic treatment are more difficult and less successful to manage because comorbid conditions and poor performance status are more prevalent, decreasing the tolerance to therapy and increasing the frequency of side effects. This age effect is highlighted by the dramatically less favorable outcome in older than younger patients with acute myeloid leukemia with similar "favorable" cytogenetic changes. In addition, in acute and subacute myeloid leukemia in older patients, the disease is intrinsically more resistant to therapy. Overexpression of drug resistance genes and unfavorable genetic mutations are more prevalent in older patients and provide evidence that acute myeloid leukemia is often qualitatively different in these patients. The gradient of age effects is continuous; the frequency of poor outcome increasing by decade (or less). The decline in survival becomes especially steep as quinquagenarians (50-year-olds) age to nonagenarians (90-year-olds). Although improved drug schedules have led to significant improvements in event-free survival in younger patients, these improvements have been far less evident in older patients. New approaches, especially the development of drugs aimed at new targets, will be required to obtain a high frequency of long-term remissions in older patients. Agents that reverse inherent cellular drug resistance, farnesyltransferase inhibitors, BCL-2 inhibitors, and [[FLT3]] inhibitors are early examples of such approaches.
|mesh-terms=* Aged
* Aging
* Bone Marrow Diseases
* Cytogenetics
* Hematopoietic Stem Cells
* Humans
* Leukemia, Myeloid
* Myelodysplastic Syndromes
* Myeloproliferative Disorders

|full-text-url=https://sci-hub.do/10.1053/j.seminoncol.2003.12.029
}}
{{medline-entry
|title=Regulation of dendritic cell expansion in aged athymic nude mice by [[FLT3]] ligand.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/15036393
|abstract=This report describes age-related alterations of dendritic cells (DC) distribution in nude athymic mice in vivo and reversal of certain age-dependent defects by an in vivo administration of hematopoietic growth factor [[FLT3]] ligand ([[FLT3]]L). There are decreased percentages of CD11c( ) DC in the bone marrow and spleen and a reduced expression of MHC class II and [[CD86]] molecules on DC in old nude mice. The decreased levels of CD11c( ) DC were due to the CD8alpha(-) DC subset. The distribution of CD11c( ) CD8alpha( ) DC in the lymphoid tissues was not different in young and old mice. The effect of in vivo administration of [[FLT3]]L on the generation and distribution of DC in the lymphoid tissues in young and old nude mice was also evaluated. Although, [[FLT3]]L had a higher inductive potential on the expansion of DC from the bone marrow in the elderly mice, the total level of CD11c( ) DC in the young animals was still significantly higher as compared to the old animals. Interestingly, [[FLT3]]L induced a pronounced redistribution and accumulation of MHC class II( ) DC in the lymphoid tissues in old mice, markedly increased the accumulation of CD8alpha(-) DC in the bone marrow in both young and old nude mice, and elevated both CD8alpha(-) and CD8alpha( ) DC in the spleen in young mice. However, only the level of CD8alpha( ) DC was up regulated in the spleen in old athymic mice after [[FLT3]]L-based therapy. In summary, abnormalities in DC generation and distribution in old athymic mice could be, in part, circumvented by the in vivo administration of [[FLT3]]L.
|mesh-terms=* Aging
* Animals
* Antigens, CD
* B7-2 Antigen
* Bone Marrow
* CD11c Antigen
* CD8 Antigens
* Cell Division
* Dendritic Cells
* Flow Cytometry
* Histocompatibility Antigens Class II
* Male
* Membrane Glycoproteins
* Membrane Proteins
* Mice
* Mice, Nude
* Spleen

|full-text-url=https://sci-hub.do/10.1016/j.exger.2004.01.003
}}
{{medline-entry
|title=[[FLT3]], RAS, and [[TP53]] mutations in elderly patients with acute myeloid leukemia.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11369655
|abstract=The prevalence and significance of genetic abnormalities in older patients with acute myeloid leukemia (AML) are unknown. Polymerase chain reactions and single-stranded conformational polymorphism analyses were used to examine 140 elderly AML patients enrolled in the Southwest Oncology Group study 9031 for [[FLT3]], RAS, and [[TP53]] mutations, which were found in 34%, 19%, and 9% of patients, respectively. All but one of the [[FLT3]] (46 of 47) mutations were internal tandem duplications (ITDs) within exons 11 and 12. In the remaining case, a novel internal tandem triplication was found in exon 11. [[FLT3]] ITDs were associated with higher white blood cell counts, higher peripheral blast percentages, normal cytogenetics, and less disease resistance. All RAS mutations (28 of 28) were missense point mutations in codons 12, 13, or 61. RAS mutations were associated with lower peripheral blast and bone marrow blast percentages. Only 2 of 47 patients with [[FLT3]] ITDs also had a RAS mutation, indicating a significant negative association between [[FLT3]] and RAS mutations (P =.0013). Most [[TP53]] mutations (11 of 12) were missense point mutations in exons 5 to 8 and were associated with abnormal cytogenetics, especially abnormalities in both chromosomes 5 and 7. [[FLT3]] and RAS mutations were not associated with inferior clinical outcomes, but [[TP53]] mutations were associated with a worse overall survival (median 1 versus 8 months, P =.0007). These results indicate that mutations in [[FLT3]], RAS, or [[TP53]] are common in older patients with AML and are associated with specific AML phenotypes as defined by laboratory values, cytogenetics, and clinical outcomes. (Blood. 2001;97:3589-3595)
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Exons
* Gene Frequency
* Genes, ras
* Humans
* Leukemia, Myeloid, Acute
* Middle Aged
* Mutation
* Polymerase Chain Reaction
* Polymorphism, Single-Stranded Conformational
* Prognosis
* Proto-Oncogene Proteins
* Receptor Protein-Tyrosine Kinases
* Tumor Suppressor Protein p53
* fms-Like Tyrosine Kinase 3

|full-text-url=https://sci-hub.do/10.1182/blood.v97.11.3589
}}