inconclusive. It could identify an aberration segregating in the family, or, as in our case, reveal a (potential) founding mutation for FPD/AML. Vigilance in identifying a RUNX1 mutation in patients suspected of FPD/AML is required as allogenic SCT is often the only potentially curative treatment. Given clinical heterogeneity of the disorder, candidate sibling donors should then be investigated for being carrier of the abnormality. Furthermore, a de novo 21q RUNX1 translocation, when present in the germ line of a carrier could be transmitted to the next generation, and could result in FPD/AML, but also in chromosomal unbalanced offspring depend- ing on which derivative chromosomes are segregating. CONFLICT OF INTEREST The authors declare no conflict of interest. ACKNOWLEDGEMENTS We thank the patients and family members who participated in this study, as well as the technicians of the section Genome Diagnostics of the Department of Medical Genetics for excellent technical support. Eric Borst and Richard Zewald are acknowledged for the initial sequencing experiments. Nine Knoers, Dick Lindhout, Tom Letteboer, Lars van der Veken (UMC Utrecht) and Marella de Bruijn (University of Oxford, United Kingdom) are particularly thanked for critically reading the manuscript and useful suggestions. Ivo Renkens is thanked for SOLiD sequencing and Edwin Cuppen for facilitating GWLMPS. A Buijs 1 , M Poot 1 , S van der Crabben 1 , B van der Zwaag 1 , E van Binsbergen 1 , MJ van Roosmalen 1 , M Tavakoli-Yaraki 1 , O de Weerdt 2 , HK Nieuwenhuis 3 , M van Gijn 1 and WP Kloosterman 1 1 Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands; 2 Department of Internal Medicine, St Antonius Hospital, Nieuwegein, The Netherlands and 3 Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands; E-mail: a.buijs@umcutrecht.nl. REFERENCES 1 Song WJ, Sullivan MG, Legare RD, Hutchings S, Tan X, Kufrin D et al. 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The mouse Runx1 þ 23 hematopoietic stem cell enhancer confers hematopoietic specificity to both Runx1 promoters. Blood 2009; 113: 5121–5124. 15 Liu L, Ishihara K, Ichimura T, Fujita N, Hino S, Tomita S et al. MCAF1/AM is involved in Sp1-mediated maintenance of cancer-associated telomerase activity. J Biol Chem 2009; 284: 5165–5174. Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu) Effects of L-leucine in 5q- syndrome and other RPS14-deficient erythroblasts Leukemia (2012) 26, 2154–2158; doi:10.1038/leu.2012.82 The 5q- syndrome is the most distinct of all the myelodysplastic syndromes (MDS) with a clear genotype/phenotype relationship. The RPS14 gene, encoding a ribosomal protein and mapping to the commonly deleted region (CDR) of the 5q- syndrome, 1 shows haploinsufficiency in the CD34 þ cells of patients with this disorder. 2,3 The genes in the 5q- syndrome CDR were studied by an RNA-mediated interference-based approach and it was shown that haploinsufficiency of RPS14 in normal CD34 þ cells resulted in a block in erythroid differentiation with relative preservation of megakaryocyte differentiation, suggesting that RPS14 haplo- insufficiency is the probable cause of the erythroid defect in this disorder. 3 Several lines of converging evidence suggest that p53 activation secondary to ribosomal haploinsufficiency is the mechanism that underlies the anemia in the 5q- syndrome. 4,5 The bone marrow cells of patients with the 5q- syndrome show a block in the processing of pre-ribosomal RNA 3 and the CD34 þ cells of these patients show deregulation of multiple ribosomal protein genes and genes involved in the control of translation. 6 These data suggest that the 5q- syndrome represents a disorder of aberrant ribosome biogenesis. 3,6 Erythroid progenitor cells have a very high rate of proliferation and a requirement for massive globin synthesis, thus necessitating a very high level of ribosome biogenesis and ribosomal activity. This may explain the particular sensitivity of the erythroid lineage to reduced expression levels of ribosomal proteins. 5 In this study, we have first investigated the effects of RPS14 haploinsufficiency on human erythropoiesis using an RPS14 short Accepted article preview online 20 March 2012; advance online publication, 18 May 2012 Letters to the Editor 2154 Leukemia (2012) 2142 – 2158 & 2012 Macmillan Publishers Limited