-
Clinical evolution, genetic landscape and trajectories of clonal hematopoiesis in SAMD9/SAMD9L syndromesSahoo, Sushree S ...Germline SAMD9 and SAMD9L mutations (SAMD9/9Lmut) predispose to myelodysplastic syndromes (MDS) with propensity for somatic rescue. In this study, we investigated a clinically annotated pediatric MDS ... cohort (n = 669) to define the prevalence, genetic landscape, phenotype, therapy outcome and clonal architecture of SAMD9/9L syndromes. In consecutively diagnosed MDS, germline SAMD9/9Lmut accounted for 8% and were mutually exclusive with GATA2 mutations present in 7% of the cohort. Among SAMD9/9Lmut cases, refractory cytopenia was the most prevalent MDS subtype (90%); acquired monosomy 7 was present in 38%; constitutional abnormalities were noted in 57%; and immune dysfunction was present in 28%. The clinical outcome was independent of germline mutations. In total, 67 patients had 58 distinct germline SAMD9/9Lmut clustering to protein middle regions. Despite inconclusive in silico prediction, 94% of SAMD9/9Lmut suppressed HEK293 cell growth, and mutations expressed in CD34+ cells induced overt cell death. Furthermore, we found that 61% of SAMD9/9Lmut patients underwent somatic genetic rescue (SGR) resulting in clonal hematopoiesis, of which 95% was maladaptive (monosomy 7 ± cancer mutations), and 51% had adaptive nature (revertant UPD7q, somatic SAMD9/9Lmut). Finally, bone marrow single-cell DNA sequencing revealed multiple competing SGR events in individual patients. Our findings demonstrate that SGR is common in SAMD9/9Lmut MDS and exemplify the exceptional plasticity of hematopoiesis in children.Vir: Nature medicine. - ISSN 1078-8956 (Vol. 27, iss. 10, 2021, str. 1806-1817)Vrsta gradiva - članek, sestavni del ; neleposlovje za odrasleLeto - 2021Jezik - angleškiCOBISS.SI-ID - 189208323
Avtor
Sahoo, Sushree S |
Pastor, Victor B |
Goodings, Charnise |
Voss, Rebecca K |
Kozyra, Emilia J |
Szvetnik, Amina |
Noellke, Peter |
Dworzak, Michael N. |
Stary, Jan |
Locatelli, Franco
Drugi avtorji
Gazić, Barbara |
Kavčič, Marko, medicina |
Podgornik, Helena
Teme
MDS predisposition |
SAMD9 |
SAMD9L |
somatic genetic rescue |
nagnjenost k MDS |
somatsko genetsko reševanje
![loading ... loading ...](themes/default/img/ajax-loading.gif)
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 |
---|---|
Sahoo, Sushree S | ![]() |
Pastor, Victor B | ![]() |
Goodings, Charnise | ![]() |
Voss, Rebecca K | ![]() |
Kozyra, Emilia J | ![]() |
Szvetnik, Amina | ![]() |
Noellke, Peter | ![]() |
Dworzak, Michael N. | ![]() |
Stary, Jan | ![]() |
Locatelli, Franco | ![]() |
Gazić, Barbara | 20050 |
Kavčič, Marko, medicina | 32049 |
Podgornik, Helena | 12684 |
Izberite prevzemno mesto:
Prevzem gradiva po pošti
Obvestilo
Gesla v Splošnem geslovniku COBISS
Izbira mesta prevzema
Mesto prevzema | Status gradiva | Rezervacija |
---|
Prosimo, počakajte trenutek.