|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
5
|
|
pubmed:dateCreated |
2011-5-10
|
|
pubmed:abstractText |
Interleukin-7 receptor ? (IL7R) is required for normal lymphoid development. Loss-of-function mutations in this gene cause autosomal recessive severe combined immune deficiency. Here, we describe somatic gain-of-function mutations in IL7R in pediatric B and T acute lymphoblastic leukemias. The mutations cause either a serine-to-cysteine substitution at amino acid 185 in the extracellular domain (4 patients) or in-frame insertions and deletions in the transmembrane domain (35 patients). In B cell precursor leukemias, the mutations were associated with the aberrant expression of cytokine receptor-like factor 2 (CRLF2), and the mutant IL-7R proteins formed a functional receptor with CRLF2 for thymic stromal lymphopoietin (TSLP). Biochemical and functional assays reveal that these IL7R mutations are activating mutations conferring cytokine-independent growth of progenitor lymphoid cells. A cysteine, included in all but three of the mutated IL-7R alleles, is essential for the constitutive activation of the receptor. This is the first demonstration of gain-of-function mutations of IL7R. Our current and recent observations of mutations in IL7R and CRLF2, respectively suggest that the addition of cysteine to the juxtamembranous domains is a general mechanism for mutational activation of type I cytokine receptors in leukemia.
|
|
pubmed:commentsCorrections |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
May
|
|
pubmed:issn |
1540-9538
|
|
pubmed:author |
pubmed-author:BandapalliObul ROR,
pubmed-author:BassoGiuseppeG,
pubmed-author:BercovichDaniD,
pubmed-author:BiondiAndreaA,
pubmed-author:CarioGunnarG,
pubmed-author:CazzanigaGiovanniG,
pubmed-author:GanmoreIthamarI,
pubmed-author:IzraeliShaiS,
pubmed-author:KulozikAndreas EAE,
pubmed-author:MuckenthalerMartina UMU,
pubmed-author:PalmiChiaraC,
pubmed-author:SchrappeMartinM,
pubmed-author:ShochatChenC,
pubmed-author:StanullaMartinM,
pubmed-author:TalNoaN,
pubmed-author:te KronnieGeertruyG
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
9
|
|
pubmed:volume |
208
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
901-8
|
|
pubmed:dateRevised |
2011-11-9
|
|
pubmed:meshHeading |
pubmed-meshheading:21536738-Adolescent,
pubmed-meshheading:21536738-Amino Acid Substitution,
pubmed-meshheading:21536738-Cell Line,
pubmed-meshheading:21536738-Child,
pubmed-meshheading:21536738-Child, Preschool,
pubmed-meshheading:21536738-Cytokines,
pubmed-meshheading:21536738-Female,
pubmed-meshheading:21536738-Humans,
pubmed-meshheading:21536738-Lymphoid Progenitor Cells,
pubmed-meshheading:21536738-Male,
pubmed-meshheading:21536738-Mutation,
pubmed-meshheading:21536738-Precursor Cell Lymphoblastic Leukemia-Lymphoma,
pubmed-meshheading:21536738-Protein Structure, Tertiary,
pubmed-meshheading:21536738-Receptors, Cytokine,
pubmed-meshheading:21536738-Receptors, Interleukin-7
|
|
pubmed:year |
2011
|
|
pubmed:articleTitle |
Gain-of-function mutations in interleukin-7 receptor-? (IL7R) in childhood acute lymphoblastic leukemias.
|
|
pubmed:affiliation |
Childhood Leukemia Research Institute and Department of Pediatric Hemato-Oncology, Sheba Medical Center, Tel Hashomer, Ramat Gan 52621, Israel.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
