Does cytogenetic mosaicism in CD 34 CD 38 low cells reflect the persistence of normal

cells, and provided persuasive evidence that the thymosin 4 and neurogranin transcripts are derived from platelets. The significance of detecting -globin mRNA in their preparations still needs to be resolved, and if platelet-derived, will likely require confirmation by in situ detection methods. However, Gnatenko and colleagues indirectly addressed this issue by isolating total RNA from whole blood and concluded that the globin transcripts observed in their platelet preparations were not supported by erythrocyte contaminant estimates.1 Based on serial analysis of gene expression (SAGE) results, which preferentially targets abundant mRNAs, the commentary also underscored the author’s conclusions that the vast majority of messages in platelets are mitochondrially derived.1,4 We do not argue this point. Indeed, mitochondrial RNAs are continuously transcribed, in contrast to other platelet transcripts, and generate multiple polyadenylated transcripts from individual genes accounting for their enhanced detection by SAGE.1 An important point, however, is that the mitochondrial genome encodes only 13 mRNAs and 2 rRNAs.1 Platelets contain over 2000 individual mRNA species,1-3 including well-known messages for the IIb and 3 integrin subunits,8,9 that were not detected by SAGE.1 Thus, although they are more abundant, mitochondrially derived transcripts represent a minute fraction ( 0.01%) of the mRNA species pool present in human platelets.1-3 There are numerous examples in which the identification of nonmitochondrial mRNAs in platelets has generated important physiologic insights regarding the characterization and functional significance of corresponding proteins.1-3,6,7,9,10 Although the total RNA in human platelets is at least 100-fold less than in leukocytes,10 platelet mRNAs are diverse, polyadenylated, distributed in a fashion that is influenced by cytoskeletal and RNA-binding proteins, and differentially translated in response to outside-in signals.1-3,6-8,10 In addition to mitochondrial transcripts, many others are basally present.1-3,6-10 Characterization of the platelet transcriptome, and the proteins that it encodes, will undoubtedly increase our understanding of platelet and megakaryocyte physiology and behavior in health and disease.