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000304246 1001_ $$00000-0002-4782-5718$$aMcLoughlin, Matthew A$$b0
000304246 245__ $$aTelomere attrition becomes an instrument for clonal selection in aging hematopoiesis and leukemogenesis.
000304246 260__ $$aLondon$$bMacmillan Publishers Limited, part of Springer Nature$$c2025
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000304246 520__ $$aThe mechanisms through which mutations in splicing factor genes drive clonal hematopoiesis (CH) and myeloid malignancies, and their close association with advanced age, remain poorly understood. Here we show that telomere maintenance plays an important role in this phenomenon. First, by studying 454,098 UK Biobank participants, we find that, unlike most CH subtypes, splicing-factor-mutant CH is more common in those with shorter genetically predicted telomeres, as is CH with mutations in PPM1D and the TERT gene promoter. We go on to show that telomere attrition becomes an instrument for clonal selection in advanced age, with splicing factor mutations 'rescuing' HSCs from critical telomere shortening. Our findings expose the lifelong influence of telomere maintenance on hematopoiesis and identify a potential shared mechanism through which different splicing factor mutations drive leukemogenesis. Understanding the mechanistic basis of these observations can open new therapeutic avenues against splicing-factor-mutant CH and hematological or other cancers.
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000304246 7001_ $$aCheloor Kovilakam, Sruthi$$b1
000304246 7001_ $$00000-0001-7246-5198$$aDunn, William G$$b2
000304246 7001_ $$aGu, Muxin$$b3
000304246 7001_ $$00009-0001-2939-0896$$aTobin, Jake$$b4
000304246 7001_ $$00000-0002-2282-1403$$aPershad, Yash$$b5
000304246 7001_ $$00000-0003-3989-9167$$aWilliams, Nicholas$$b6
000304246 7001_ $$00000-0002-3486-3168$$aLeongamornlert, Daniel$$b7
000304246 7001_ $$aDawson, Kevin$$b8
000304246 7001_ $$aBond, Laura$$b9
000304246 7001_ $$aMarando, Ludovica$$b10
000304246 7001_ $$aWen, Sean$$b11
000304246 7001_ $$00000-0001-5129-7295$$aWilson, Rachael$$b12
000304246 7001_ $$aValenzano, Giampiero$$b13
000304246 7001_ $$aSymeonidou, Vasiliki$$b14
000304246 7001_ $$aRak, Justyna$$b15
000304246 7001_ $$aDamaskou, Aristi$$b16
000304246 7001_ $$00000-0002-3134-1276$$aGozdecka, Malgorzata$$b17
000304246 7001_ $$aLiu, Xiaoxuan$$b18
000304246 7001_ $$aBarcena, Clea$$b19
000304246 7001_ $$00000-0003-3399-346X$$aNomdedeu, Josep$$b20
000304246 7001_ $$aCosteas, Paul$$b21
000304246 7001_ $$aDimitriou, Ioannis D$$b22
000304246 7001_ $$00000-0002-8690-4988$$aFiorillo, Edoardo$$b23
000304246 7001_ $$00000-0002-6047-4625$$aOrrù, Valeria$$b24
000304246 7001_ $$ade Almeida, Jose Guilherme$$b25
000304246 7001_ $$aMcKerrell, Thomas$$b26
000304246 7001_ $$aCullen, Matthew$$b27
000304246 7001_ $$00000-0003-4863-761X$$aMohorianu, Irina$$b28
000304246 7001_ $$aFoukaneli, Theodora$$b29
000304246 7001_ $$00000-0001-9277-4553$$aWarren, Alan J$$b30
000304246 7001_ $$aWong, Chi$$b31
000304246 7001_ $$aFollows, George$$b32
000304246 7001_ $$aGodfrey, Anna L$$b33
000304246 7001_ $$aGudgin, Emma$$b34
000304246 7001_ $$00000-0002-7414-1995$$aCucca, Francesco$$b35
000304246 7001_ $$00000-0003-3516-3072$$aMcKinney, Eoin$$b36
000304246 7001_ $$00000-0002-5946-5238$$aBaxter, E Joanna$$b37
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000304246 7001_ $$00000-0003-3792-4058$$aMitchell, Jonathan$$b39
000304246 7001_ $$00000-0003-0715-1402$$aWiseman, Daniel$$b40
000304246 7001_ $$00000-0001-5824-9595$$aBick, Alexander G$$b41
000304246 7001_ $$00000-0001-7794-610X$$aFabre, Margarete$$b42
000304246 7001_ $$00000-0002-7793-6291$$aQuiros, Pedro M$$b43
000304246 7001_ $$00000-0001-7122-4608$$aNangalia, Jyoti$$b44
000304246 7001_ $$aKar, Siddhartha$$b45
000304246 7001_ $$00000-0003-4337-8022$$aVassiliou, George S$$b46
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