Publications by authors named "S R Killick"
Article Synopsis
- - Dyskeratosis congenita (DC) is a rare inherited condition that leads to bone marrow failure and is largely linked to mutations affecting telomere biology, with about 35% of cases having unidentified genetic causes.
- - Research on a wide range of DC and 'DC-like' cases uncovered new pathogenic variants, including findings in the novel X-linked gene POLA1 and in known genes POT1 and ZCCHC8, enhancing the understanding of the genetic basis of these disorders.
- - Functional studies indicated that the new variants in POLA1 and POT1 disrupt crucial protein interactions that are essential for telomere maintenance, while ZCCHC8 variants lead to inflammation in patients, thereby contributing to the understanding of
Pancytopenia with hypocellular bone marrow is the hallmark of aplastic anaemia (AA) and the diagnosis is confirmed after careful evaluation, following exclusion of alternate diagnosis including hypoplastic myelodysplastic syndromes. Emerging use of molecular cyto-genomics is helpful in delineating immune mediated AA from inherited bone marrow failures (IBMF). Camitta criteria is used to assess disease severity, which along with age and availability of human leucocyte antigen compatible donor are determinants for therapeutic decisions.
View Article and Find Full Text PDFClonal tracking of cells using somatic mutations permits exploration of clonal dynamics in human disease. Here, we perform whole genome sequencing of 323 haematopoietic colonies from 10 individuals with the inherited ribosomopathy Shwachman-Diamond syndrome to reconstruct haematopoietic phylogenies. In ~30% of colonies, we identify mutually exclusive mutations in TP53, EIF6, RPL5, RPL22, PRPF8, plus chromosome 7 and 15 aberrations that increase SBDS and EFL1 gene dosage, respectively.
View Article and Find Full Text PDFTo determine the survival benefit of allogeneic hematopoietic cell transplantation (allo-HCT) in chronic myelomonocytic leukemias (CMML), we assembled a retrospective cohort of CMML patients 18-70 years old diagnosed between 2000 and 2014 from an international CMML dataset (n = 730) and the EBMT registry (n = 384). The prognostic impact of allo-HCT was analyzed through univariable and multivariable time-dependent models and with a multistate model, accounting for age, sex, CMML prognostic scoring system (low or intermediate-1 grouped as lower-risk, intermediate-2 or high as higher-risk) at diagnosis, and AML transformation. In univariable analysis, lower-risk CMMLs had a 5-year overall survival (OS) of 20% with allo-HCT vs 42% without allo-HCT (P < .
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