FLT3 internal tandem duplication mutations are rare in agnogenic myeloid metaplasia

Abu-Duhier, Faisal; Goodeve, Anne; Wilson, Gill; Carr, Rory S.; Peake, I. R.; Reilly, John T.

doi:10.1182/blood-2002-02-0536

Cited by 12 publications

(5 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mutations consisted of ITDs of the JM coding sequence, primarily involving exon 14, but occasionally involving intron 14 and exon 15 (see Abu‐Duhier et al, 2001b). The FLT3 ITD has subsequently been found in a high proportion of AML patients (Kiyoi et al , 1999; Abu‐Duhier et al, 2000; Kottaridis et al, 2001) and in myelodysplastic syndromes (3%), but not in CML, IMF or normal haematopoietic tissue (Yokota et al , 1997; Ishii et al , 1999; Abu‐Duhier et al, 2002). In addition, FLT3 ITD mutations may emerge during transformation of MDS or at relapse of AML, suggesting that they promote leukaemic progression (Horiike et al , 1997; Nakano et al , 1999).…”

Section: Discussionmentioning

confidence: 99%

“…In order to clarify the frequency and nature of RTK class III mutations in IMF, we have extended our preliminary studies of FLT3 ITD screening in IMF (Abu‐Duhier et al, 2002) by screening the FLT3 gene for exon 9, 11 and 20 mutations, as well as the entire coding region of the C‐FMS and C‐KIT genes, in a large number of well‐characterized cases.…”

mentioning

confidence: 99%

“…Internal tandem duplication mutations (ITD) of the FLT3 JM domain, for example, have been reported in approximately 20% of patients with acute myeloid leukaemia (AML) (Kiyoi et al , 1999; Abu‐Duhier et al, 2000; Kottaridis et al, 2001) and appear to be the most important independent prognostic factor. FLT3 ITDs have also been reported in a small number of patients with myelodysplastic syndrome, but not in chronic myeloid leukaemia (CML), IMF or normal haematopoetic tissue (Yokota et al , 1997; Ishii et al , 1999; Abu‐Duhier et al, 2002). Recently, mutations in exon 20 (Asp835) have been reported in 7% of AML patients, suggesting that FLT3 is the target gene most commonly mutated in AML (Abu‐Duhier et al, 2001a; Yamamoto et al, 2001).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Mutational analysis of class III receptor tyrosine kinases (C‐KIT, C‐FMS, FLT3) in idiopathic myelofibrosis

et al. 2003

Self Cite

View full text Add to dashboard Cite

Summary. Genomic DNA from patients with idiopathic myelofibrosis (IMF) was screened by polymerase chain reaction (PCR) and conformation sensitive gel electrophoresis (CSGE) for mutations in the C-KIT gene (60 patients), as well as the C-FMS and FLT3 genes (40 patients). Intronic primers were used to amplify the entire coding region of both the C-KIT and C-FMS genes, and selected regions of the FLT3 gene. CSGE and direct DNA sequencing detected all previously reported as well as several novel polymorphisms in each of the genes. A novel c-fms exon 9 mutation (Gly413Ser) was detected in two patients. Its functional significance remains to be determined. The c-kit mutation Asp52Asn, previously described in two of six IMF patients in Japan, was not detected in this study. In addition, the reported c-fms mutations involving codons 301 and 969 were not identified. Therefore, in contrast to acute myeloid leukaemia, mutations in RTKs class III do not appear to play a significant pathogenetic role in idiopathic myelofibrosis.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Mutational analysis of class III receptor tyrosine kinases (C‐KIT, C‐FMS, FLT3) in idiopathic myelofibrosis

et al. 2003

Self Cite

View full text Add to dashboard Cite

show abstract

“…44 The mutation rate is low in MDS and ALL, and the mutation has not been found in myeloma, lymphoma, CLL, or the myeloproliferative disorders. 78,116,117 Any attempt to estimate the incidence of FLT3/ITD mutations in AML patients will be influenced by a number of factors. The population being studied is clearly important, as the mutation incidence varies significantly between AML subtypes, particularly those subgroups defined by cytogenetic abnormalities.…”

Section: Incidence Of Flt3/itd Mutations In Amlmentioning

confidence: 99%

FLT3: ITDoes matter in leukemia

2003

View full text Add to dashboard Cite

FMS-like tyrosine kinase-3 (FLT3), a receptor tyrosine kinase, is important for the development of the hematopoietic and immune systems. Activating mutations of FLT3 are now recognized as the most common molecular abnormality in acute myeloid leukemia, and FLT3 mutations may play a role in other hematologic malignancies as well. The poor prognosis of patients harboring these mutations renders FLT3 an obvious target of therapy. This review summarizes the data on the molecular biology and clinical impact of FLT3 mutations, as well as the therapeutic potential of several small-molecule FLT3 inhibitors currently in development.

show abstract

“…FLT3 mutations are found in up to approximately 20-30% of acute myeloid leukemia (AML) patients, are associated with a normal karyotype, and are more frequently found in adults compared to children, with a decreasing incidence above 60 years of age [4][5][6][7]. The majority occur as internal tandem duplications (ITDs); approximately 7-10% are point mutations in the tyrosine kinase domain (TKD) at codon 835 or 836 [4,8,9]. FLT3 internal tandem duplications (FLT3-ITDs) are in-frame replicated sequences in the juxtamembrane domain of the FLT3 receptor (some extend into TKD1).…”

Section: Introductionmentioning

confidence: 99%

The Clinical Utility of FLT3 Mutation Testing in Acute Leukemia: A Canadian Consensus

Bergeron,

Capo-Chichi,

Tsui

et al. 2023

Current Oncology

View full text Add to dashboard Cite

FMS-like tyrosine kinase 3 (FLT3) mutations are detected in approximately 20–30% of patients with acute myeloid leukemia (AML), with the presence of a FLT3 internal tandem duplication (FLT3-ITD) mutation being associated with an inferior outcome. Assessment of FLT3 mutational status is now essential to define optimal upfront treatment in both newly diagnosed and relapsed AML, to support post-induction allogeneic hematopoietic stem cell transplantation (alloSCT) decision-making, and to evaluate treatment response via measurable (minimal) residual disease (MRD) evaluation. In view of its importance in AML diagnosis and management, the Canadian Leukemia Study Group/Groupe canadien d’étude sur la leucémie (CLSG/GCEL) undertook the development of a consensus statement on the clinical utility of FLT3 mutation testing, as members reported considerable inter-center variability across Canada with respect to testing availability and timing of use, methodology, and interpretation. The CLSG/GCEL panel identified key clinical and hematopathological questions, including: (1) which patients should be tested for FLT3 mutations, and when?; (2) which is the preferred method for FLT3 mutation testing?; (3) what is the clinical relevance of FLT3-ITD size, insertion site, and number of distinct FLT3-ITDs?; (4) is there a role for FLT3 analysis in MRD assessment?; (5) what is the clinical relevance of the FLT3-ITD allelic burden?; and (6) how should results of FLT3 mutation testing be reported? The panel followed an evidence-based approach, taken together with Canadian clinical and laboratory experience and expertise, to create a consensus document to facilitate a more uniform approach to AML diagnosis and treatment across Canada.

show abstract

FLT3 internal tandem duplication mutations are rare in agnogenic myeloid metaplasia

Cited by 12 publications

References 5 publications

Mutational analysis of class III receptor tyrosine kinases (C‐KIT, C‐FMS, FLT3) in idiopathic myelofibrosis

Mutational analysis of class III receptor tyrosine kinases (C‐KIT, C‐FMS, FLT3) in idiopathic myelofibrosis

FLT3: ITDoes matter in leukemia

The Clinical Utility of FLT3 Mutation Testing in Acute Leukemia: A Canadian Consensus

Contact Info

Product

Resources

About