FLT3 mutations in childhood acute lymphoblastic leukemia at first relapse

Wellmann, Sven; Moderegger, E; Zelmer, Andrea; Bettkober, Maxi; Stackelberg, Arend von; Henze, Günter; Seeger, Karl

doi:10.1038/sj.leu.2403655

Cited by 9 publications

(7 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The incidence at presentation compares well with two other previous studies (6,24), and we show a similar incidence at relapse. Four FLT3 mutations were identified in total, with an incidence of 10% at diagnosis and 2% at relapse, which is in keeping with other studies (7,8,(25)(26)(27). One patient had the characteristic D835E mutation, whereas three others had insertion/deletion mutations of the juxtamembrane region.…”

Section: Discussionsupporting

confidence: 67%

Mutation of Genes Affecting the RAS Pathway Is Common in Childhood Acute Lymphoblastic Leukemia

Case¹,

Matheson²,

Minto³

et al. 2008

Cancer Research

125

140

View full text Add to dashboard Cite

Deregulation of the RAS-RAF-mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK signaling cascade is often caused by somatic mutations in genes encoding proteins which influence the activity of this pathway and include NRAS, KRAS2, FLT3, PTPN11, and BRAF. We report the first comprehensive mutational screen of key exons of these genes in a large cohort of unselected acute lymphoblastic leukemia (ALL) cases at diagnosis (n = 86) and in a more selected cohort at disease recurrence (n = 47) using the sensitive method of denaturing high-performance liquid chromatography. We show that somatic mutations that deregulate the pathway constitute one of the most common genetic aberrations in childhood ALL (cALL), being found in 35% of diagnostic and 25% of relapse samples. In matched presentation/relapse pairs, mutations predominating at relapse could be shown to be present at very low levels at diagnosis using allele-specific PCR, thus implicating the mutated clone in disease progression. Importantly, in primary samples, we show that mutations are associated with activated ERK and differential cytotoxicity to MEK-ERK inhibitors was shown for some patients. Inhibitors of the pathway, which are currently undergoing clinical trial, may be a novel therapeutic option for cALL, particularly at relapse. [Cancer Res 2008;68(16):6803-9]

show abstract

Section: Discussionsupporting

confidence: 67%

Mutation of Genes Affecting the RAS Pathway Is Common in Childhood Acute Lymphoblastic Leukemia

Case¹,

Matheson²,

Minto³

et al. 2008

Cancer Research

125

140

View full text Add to dashboard Cite

show abstract

“…19 Constitutive activation of the FLT3 receptor tyrosine kinase can occur in a significant proportion of leukemia patients as a result of somatic ITDs, point mutations (D835/I836), or less common chromosomal rearrangements. 16,20 Somatic alterations involving the FLT3 locus have been shown to be of prognostic importance in acute leukemia, and there are potent, specific FLT3 kinase inhibitors in late-stage clinical trials. 21 We observed 89 alterations targeting FLT3 in 84 specimens.…”

Section: Clinical Experience To Datementioning

confidence: 99%

Integrated genomic DNA/RNA profiling of hematologic malignancies in the clinical setting

He¹,

Abdel‐Wahab²,

Nahas³

et al. 2016

Blood

261

219

View full text Add to dashboard Cite

show abstract

“…2 C ): one where the target protein was high at diagnosis and decreased up to 10-fold in relapse (such as for ROR1 and NCR3LG1), and another where the target was low at diagnosis and increased up to 100-fold at relapse (such as for FLT3 and PDGFRB). FLT3 has previously been observed to be overexpressed and/or mutated in ALL and acute myeloid leukemia (AML) ( 16 , 17 ). ROR1 also represents a major target of interest in ALL, chronic lymphocytic leukemia (CLL), and other leukemias ( 18 – 20 ).…”

Section: Resultsmentioning

confidence: 99%

Highly multiplexed and quantitative cell-surface protein profiling using genetically barcoded antibodies

Pollock

Mou

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

SignificanceNext-generation sequencing (NGS) has allowed the comprehensive study of the genome and transcriptome. However, a similarly broad, highly multiplexed, and inexpensive method for proteomics using NGS remains elusive. Here, we describe a phage display-based method using preselected antibodies that are genetically encoded and capable of simultaneous profiling of hundreds of cell-surface targets on cells in culture or singly at low cost and without the need for chemical conjugation to purified antibodies. We use the method to identify cell-surface proteins that change in cancer cells, some of which are coordinately regulated and could lead to new biomarkers and cancer targets.

show abstract

FLT3 mutations in childhood acute lymphoblastic leukemia at first relapse

Cited by 9 publications

References 9 publications

Mutation of Genes Affecting the RAS Pathway Is Common in Childhood Acute Lymphoblastic Leukemia

Mutation of Genes Affecting the RAS Pathway Is Common in Childhood Acute Lymphoblastic Leukemia

Integrated genomic DNA/RNA profiling of hematologic malignancies in the clinical setting

Highly multiplexed and quantitative cell-surface protein profiling using genetically barcoded antibodies

Contact Info

Product

Resources

About