E-viri
Recenzirano
Odprti dostop
-
Skokowa, Julia; Steinemann, Doris; Katsman-Kuipers, Jenny E.; Zeidler, Cornelia; Klimenkova, Olga; Klimiankou, Maksim; Ünalan, Murat; Kandabarau, Siarhei; Makaryan, Vahagn; Beekman, Renee; Behrens, Kira; Stocking, Carol; Obenauer, Julia; Schnittger, Susanne; Kohlmann, Alexander; Valkhof, Marijke G.; Hoogenboezem, Remco; Göhring, Gudrun; Reinhardt, Dirk; Schlegelberger, Brigitte; Stanulla, Martin; Vandenberghe, Peter; Donadieu, Jean; Zwaan, C. Michel; Touw, Ivo P.; van den Heuvel-Eibrink, Marry M.; Dale, David C.; Welte, Karl
Blood, 04/2014, Letnik: 123, Številka: 14Journal Article
Severe congenital neutropenia (CN) is a preleukemic bone marrow failure syndrome with a 20% risk of evolving into leukemia or myelodysplastic syndrome (MDS). Patterns of acquisition of leukemia-associated mutations were investigated using next-generation deep-sequencing in 31 CN patients who developed leukemia or MDS. Twenty (64.5%) of the 31 patients had mutations in RUNX1. A majority of patients with RUNX1 mutations (80.5%) also had acquired CSF3R mutations. In contrast to their high frequency in CN patients who developed leukemia or MDS, RUNX1 mutations were found in only 9 of 307 (2.9%) patients with de novo pediatric acute myeloid leukemia. A sequential analysis at stages prior to overt leukemia revealed RUNX1 mutations to be late events in leukemic transformation. Single-cell analyses in 2 patients showed that RUNX1 and CSF3R mutations were present in the same malignant clone. Functional studies demonstrated elevated granulocyte colony-stimulating factor (G-CSF)–induced proliferation with diminished myeloid differentiation of hematopoietic CD34+ cells coexpressing mutated forms of RUNX1 and CSF3R. The high frequency of cooperating RUNX1 and CSF3R mutations in CN patients suggests a novel molecular pathway of leukemogenesis: mutations in the hematopoietic cytokine receptor (G-CSFR) in combination with the second mutations in the downstream hematopoietic transcription fator (RUNX1). The detection of both RUNX1 and CSF3R mutations could be used as a marker for identifying CN patients with a high risk of progressing to leukemia or MDS. •CN/AML patients have a high frequency of CSF3R and RUNX1 mutations.•CSF3R and RUNX1 mutations induce elevated proliferation of CD34+ cells.
Avtor
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.