Novel <i>FLT3</i> point mutations within exon  14 found in patients with acute myeloid leukaemia

Stirewalt, Derek L.; Meshinchi, Soheil; Kussick, Steven J.; Sheets, Kayla M.; Pogosova-Agadjanyan, Era L.; Willman, Cheryl L.; Radich, Jerald P.

doi:10.1111/j.1365-2141.2004.04808.x

Cited by 52 publications

(48 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…16 Novel primers for Flt3 exons 14 and 15 were developed for this purpose, as previously described. 18 Cytogenetic studies were performed on G-banded preparations. 19 Fluorescent in situ hybridization (FISH) to detect the t(15;17) was performed using probes for the promyelocytic leukemia (PML) gene and the retinoic acid receptor-alpha (RARA) gene at 15q22 and 17q21, respectively (Vysis, Downers Grove, IL, USA), according to the manufacturer's instructions.…”

Section: Molecular and Cytogenetic Methodsmentioning

confidence: 99%

A distinctive nuclear morphology in acute myeloid leukemia is strongly associated with loss of HLA-DR expression and FLT3 internal tandem duplication

Kussick

Stirewalt

et al. 2004

Leukemia

View full text Add to dashboard Cite

In a 5-year survey of nonpromyelocytic/nonmonocytic acute myeloid leukemias (AMLs) diagnosed in the University of Washington Hematopathology Laboratory, we identified 19 cases containing distinctive, cup-like nuclear indentation in 10% or more of the blasts ('AML-cuplike'). Fourteen of these cases (74%) demonstrated near-complete loss of HLA-DR expression, while the other five cases showed partial loss of HLA-DR. A total of 16 of the cases (84%) demonstrated internal tandem duplication (ITD) of the Flt3 gene. When compared to a selected set of AMLs lacking this nuclear morphology, AMLcuplike was significantly more likely to lack HLA-DR and CD34 expression, to express CD123 without CD133, to have a normal karyotype, and to harbor the Flt3 ITD. To characterize AMLcuplike in an unselected series of AMLs, we analyzed 42 consecutive nonpromyelocytic/nonmonocytic AMLs diagnosed in our laboratory during a 6-month period in 2002. Strikingly, in this unselected series, there was a statistically significant coincidence of invaginated nuclear morphology, loss of HLA-DR, and presence of the Flt3 ITD beyond that expected if these three features were unrelated, suggesting that AMLs with these three features may represent a distinct AML subset.

show abstract

Section: Molecular and Cytogenetic Methodsmentioning

confidence: 99%

A distinctive nuclear morphology in acute myeloid leukemia is strongly associated with loss of HLA-DR expression and FLT3 internal tandem duplication

Kussick

Stirewalt

et al. 2004

Leukemia

View full text Add to dashboard Cite

show abstract

“…Their prevalence seems to be lower than 1% in all AML subtypes and has not yet been established in cytogenetically normal AML (CN-AML). 19,20 Lastly, a novel gain-of-function mutation (K663Q), located not in the AL but in the N-terminal part of TKD, has been recently identified in AML. 21 Interestingly, a recent study stressed the importance of functional studies, since among the different FLT3 mutations reported outside the JMD and the TKD, some were not associated with kinase activation, and did not contribute to leukemogenesis.…”

Section: Flt3mentioning

confidence: 99%

Cooperating gene mutations in acute myeloid leukemia: a review of the literature

et al. 2008

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) is a heterogeneous group of neoplastic disorders with great variability in clinical course and response to therapy, as well as in the genetic and molecular basis of the pathology. Major advances in the understanding of leukemogenesis have been made by the characterization and the study of acquired cytogenetic abnormalities, particularly reciprocal translocations observed in AML. Besides these major cytogenetic abnormalities, gene mutations also constitute key events in AML pathogenesis. In this review, we describe the contribution of known gene mutations to the understanding of AML pathogenesis and their clinical significance. To gain more insight in this understanding, we clustered these alterations in three groups: (1) mutations affecting genes that contribute to cell proliferation (FLT3, c-KIT, RAS, protein tyrosine standard phosphatase nonreceptor 11); (2) mutations affecting genes involved in myeloid differentiation (AML1 and CEBPA) and (3) mutations affecting genes implicated in cell cycle regulation or apoptosis (P53, NPM1). This nonexhaustive review aims to show how gene mutations interact with each other, how they contribute to refine prognosis and how they can be useful for risk-adapted therapeutic management of AML patients.

show abstract

“…Akin to FLT3-ITDs, FLT3-TKDs promote constitutive phosphorylation of the FLT3 protein, thereby leading to disruption of normal haematopoiesis. The third type of FLT3 alterations, point mutations in the juxtamembrane domain of the FLT3 gene, is relatively rare (Stirewalt et al, 2004;Reindl et al, 2006).…”

Section: Mutations Of the Fms-related Tyrosine Kinase 3 (Flt3) Genementioning

confidence: 99%

Clinical outcome of de novo acute myeloid leukaemia patients with normal cytogenetics is affected by molecular genetic alterations: a concise review

et al. 2007

View full text Add to dashboard Cite

SummaryNormal cytogenetics are detected pretreatment in approximately 45% of patients with de novo acute myeloid leukaemia (AML); thus this constitutes the single largest cytogenetic group of AML. Recently, molecular genetic alterations with prognostic significance have been reported in these patients. They include internal tandem duplication of the FLT3 gene, partial tandem duplication of the MLL gene, mutations of the CEBPA and NPM1 genes and aberrant expression of the BAALC, ERG and MN1 genes. Additionally, gene-expression profiling has been applied to identify prognostically relevant subgroups. Substantial progress has been made in the understanding of molecular pathways deregulated in leukaemogenesis and how these defects can be targeted by novel therapeutic compounds. Here we critically review the molecular heterogeneity among AML patients with normal cytogenetics and discuss how these data may translate into a prognostic, molecular-based treatment stratification that may improve the currently unsatisfactory outcome of these patients.

show abstract

Novel FLT3 point mutations within exon 14 found in patients with acute myeloid leukaemia

Cited by 52 publications

References 10 publications

A distinctive nuclear morphology in acute myeloid leukemia is strongly associated with loss of HLA-DR expression and FLT3 internal tandem duplication

A distinctive nuclear morphology in acute myeloid leukemia is strongly associated with loss of HLA-DR expression and FLT3 internal tandem duplication

Cooperating gene mutations in acute myeloid leukemia: a review of the literature

Clinical outcome of de novo acute myeloid leukaemia patients with normal cytogenetics is affected by molecular genetic alterations: a concise review

Contact Info

Product

Resources

About