Showing papers by "Katerina Zoi published in 2019"

PRR14L mutations are associated with chromosome 22 acquired uniparental disomy, age-related clonal hematopoiesis and myeloid neoplasia.

Abstract: Acquired uniparental disomy (aUPD, also known as copy-neutral loss of heterozygosity) is a common feature of cancer cells and characterized by extended tracts of somatically-acquired homozygosity without any concurrent loss or gain of genetic material. The presumed genetic targets of many regions of aUPD remain unknown. Here we describe the association of chromosome 22 aUPD with mutations that delete the C-terminus of PRR14L in patients with chronic myelomonocytic leukemia (CMML), related myeloid neoplasms and age-related clonal hematopoiesis (ARCH). Myeloid panel analysis identified a median of three additional mutated genes (range 1–6) in cases with a myeloid neoplasm (n = 8), but no additional mutations in cases with ARCH (n = 2) suggesting that mutated PRR14L alone may be sufficient to drive clonality. PRR14L has very limited homology to other proteins and its function is unknown. ShRNA knockdown of PRR14L in human CD34+ cells followed by in vitro growth and differentiation assays showed an increase in monocytes and decrease in neutrophils, consistent with a CMML-like phenotype. RNA-Seq and cellular localization studies suggest a role for PRR14L in cell division. PRR14L is thus a novel, biallelically mutated gene and potential founding abnormality in myeloid neoplasms.

Frequency distribution of RHD alleles among Greek donors with weak D phenotypes demonstrates a distinct pattern in central European countries.

Abstract: Dear Sir, The high immunogenicity of the Rh blood group accounts for its implication in transfusion medicine and renders it second in importance only to the ABO group. Several RHD alleles have been described and are classically classified under three broad categories: weak D, partial D and DEL. These phenotypes frequently arise from various single-nucleotide polymorphisms (SNP) in the RHD gene (Flegel, 2011). The molecular basis lies on at least 493 alleles identified so far that result in 98 RHD alleles as classified by the International Society of Blood Transfusion (ISBT). The genetic diversity caused by these mutations leads to qualitative and/or quantitative changes in the expression of the D antigen. Weak D types 1, 2 and 3 are associated with quantitative changes of presentation of a complete D-epitope, whereas in weak D type 4·2 (DAR), 11, 15 and 21, qualitative differences in D-epitope presentation, typically associated with partial D phenotypes, are apparent, and cases of allo-anti-D production have been reported (Daniels, 2005). RHD alleles differ by ethnicity with weak D frequently encountered in Caucasians, partial D in African Blacks and DEL in Asians (Flegel, 2011). Approximately 90% of weak Ds in Caucasians are weak D type 1, 2 or 3, with distributions varying among different ethnic populations (Ansart-Pirenne et al., 2004). When D antigen discrepancies arise, clinicians are faced with assigning the appropriate D antigen status so that the appropriate (RhD– or RhD+) blood products can be administered. The clinical relevance of identifying subtypes is that weak D subjects belonging to weak types 1, 2 and 3 can be treated as RhD-positive and be transfused with RhD-positive red blood cells, whereas subjects with weak D type 4·2–11 and 15 should be treated as RhD-negative (Flegel, 2011). In terms of proper donor characterisation, blood donors with weak phenotypic expression of the D antigen should be typed as RhD-positive as administration of their blood can stimulate alloimunisation when transfused in RhD-negative patients. Routine serological RhD typing cannot distinguish between weak and partial D types, but detection and classification of these