Prognostic Implications of the Presence of FLT3 Mutations in Patients with Acute Myeloid Leukemia

@article{Kottaridis2003PrognosticIO,
  title={Prognostic Implications of the Presence of FLT3 Mutations in Patients with Acute Myeloid Leukemia},
  author={Panagiotis D. Kottaridis and Rosemary E. Gale and David C. Linch},
  journal={Leukemia \& Lymphoma},
  year={2003},
  volume={44},
  pages={905 - 913}
}
Several studies have shown that mutations in the FLT3 gene are common events in AML, with approximately one third of adult patients harbouring either an internal tandem duplication in the juxtramembrane domain or a D835 mutation in the kinase domain. The majority of studies in pediatric and adult AML have shown that FLT3 mutations are powerful prognostic factors predicting for increased relapse risk and adverse overall survival. Some reports have suggested that loss of the wild type allele… 
Prognostic significance of FLT3 mutations in pediatric non-promyelocytic acute myeloid leukemia.
TLDR
New therapeutic scheme such as stem cell transplantation with more intensive conditioning just after complete remission could be applied in pediatric non-promyelocytic AML patients with the FLT3/ITD mutation.
Importance of early detection and follow-up of FLT3 mutations in patients with acute myeloid leukemia
TLDR
The results indicate an association of FLT3/ITD with the adverse outcome in AML patients treated with standard induction chemotherapy and its early detection could be helpful in clinical practice.
Internal Tandem Duplication of FLT3 Gene in Egyptian Adult Acute Myeloid and Acute Lymphoblastic Leukemia
TLDR
Evaluated the relative frequency of FLT3/ITD status in adult AML and ALL patients and its possible impact on response to treatment and overall survival found to be comparable to the literature, however in adult ALL it was much higher than that reported in literature.
Prognostic Significance of FLT3 Internal Tandem Duplication in Acute Myeloid Leukemia with Normal Karyotype
TLDR
This study demonstrated that a high ITD-AR and FLT3/ITD had major adverse impacts on the prognostic relevance for AML patients with normal karyotype.
Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype.
TLDR
It is demonstrated that NPM1+/FLT3-LM- mutations are an independent predictor for a favorable outcome in AML with normal karyotype.
Stability and prognostic influence of FLT3 mutations in paired initial and relapsed AML samples
TLDR
Interestingly, FLT3/ITD positivity was related to a significantly shorter time to relapse, most pronounced when the ITD-positive status was found at relapse, while losses may reflect ITDs in the more mature leukemic cells rather than in theLeukemic stem cell, or, alternatively, that other genetic aberrations provided a greater selective advantage.
Prevalence and Effect Evaluation of FLT3 and NPM1 Mutations in Acute Myeloid Leukemia Patients in Eastern Algeria
TLDR
According to the statistical analysis results, FLT3mut group showed shorter survival time and poor response to the induction therapy, while NPM1 was a predictor of better prognosis in the absence ofFLT3 mutations.
Targeting FLT3 Signaling in Childhood Acute Myeloid Leukemia
TLDR
Clinical outcomes for children with AML treated with maximally intensive multi-agent chemotherapy lag far behind those of children with the more common acute lymphoblastic leukemia, demonstrating continued need for new therapeutic approaches to decrease relapse risk and improve long-term survival.
[JAK2-V617F mutation in patients with myeloproliferative neoplasms: association with FLT3-ITD mutation].
TLDR
This study suggests that one activating mutation is sufficient for aberrant cell proliferation leading to malignant transformation of haematopoetic stem cell.
MRD in AML: The Role of New Techniques
TLDR
The technological advances have increased the application of MRD-based strategies to a significantly higher number of AML patients, and the information deriving from MRD assessment has been used to design individual post-remission protocols and pre-emptive treatments in patients with sub-clinical relapse.
...
...

References

SHOWING 1-10 OF 54 REFERENCES
Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia.
TLDR
The FLT3 gene mutation, whose presence is detectable only by genomic polymerase chain reaction amplification and gel electrophoresis, might serve as an important molecular marker to predict the prognosis of patients with AML.
Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis.
TLDR
Data confirm that FLT mutations represent a common alteration in adult AML and a high mutant/wt ratio in ITD-positive patients appears to have a major impact on the prognostic relevance.
Biological characteristics and prognosis of adult acute myeloid leukemia with internal tandem duplications in the Flt3 gene
TLDR
Data show that the Flt3/ITD represents an important diagnostic marker for patient prognosis, and that the presence of these mutations is associated with altered proliferative ability of progenitors in vivo and in vitro.
FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia.
TLDR
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.
Studies of FLT3 mutations in paired presentation and relapse samples from patients with acute myeloid leukemia: implications for the role of FLT3 mutations in leukemogenesis, minimal residual disease detection, and possible therapy with FLT3 inhibitors.
TLDR
The results indicate that FLT3 mutations are secondary events in leukemogenesis, are unstable, and thus should be used cautiously for the detection of minimal residual disease.
Internal tandem duplication of the FLT3 gene and clinical evaluation in childhood acute myeloid leukemia
TLDR
The results suggest that the tandem duplication in the jm domain of the FLT3 gene is not a frequent phenomenon but might be a factor of poor prognosis in childhood patients with AML.
Prognostic value of internal tandem duplication of the FLT3 gene in childhood acute myelogenous leukemia.
TLDR
FLT3/ITD was observed in 11% of childhood AML and identified to be associated with poor prognosis and a large prospective study with uniform treatment is necessary to confirm the results.
Prevalence and prognostic significance of Flt3 internal tandem duplication in pediatric acute myeloid leukemia.
TLDR
Diagnostic bone marrow specimens from 91 pediatric patients with AML were analyzed for the presence of the Flt3/ITD and its presence was the single most significant, independent prognostic factor for poor outcome in pediatric AML.
Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease.
TLDR
Besides the importance of FLT3-LM for biologic and clinical characterization of AML, its value as a marker for disease monitoring based on 120 follow-up samples of 34 patients is shown.
Tandem duplications of the FLT3 receptor gene are associated with leukemic transformation of myelodysplasia
TLDR
The fact that the accumulation of genetic events, including FLT3 duplication, correlates with leukemic transformation from antecedent myelodysplasia and with subsequent disease progression is uncovered.
...
...