Changes in megakaryopoiesis over ontogeny and their implications in health and disease

References

• Allen Graeve JL, de Alarcon PA. Megakaryocytopoiesis in the human fetus. Arch Dis Child 1989;64(4):481–484. doi:10.1136/adc.64.4_Spec_No.481.
   PubMed Web of Science ®Google Scholar
• de Alarcon PA, Graeve JL. Analysis of megakaryocyte ploidy in fetal bone marrow biopsies using a new adaptation of the feulgen technique to measure DNA content and estimate megakaryocyte ploidy from biopsy specimens. Pediatr Res 1996;39(1):166–170. doi:10.1203/00006450-199601000-00026.
   PubMed Web of Science ®Google Scholar
• Zipursky A, Brown EJ, Christensen H, Doyle J. Transient myeloproliferative disorder (transient leukemia) and hematologic manifestations of Down syndrome. Clin Lab Med 1999;19(1):157–67, vii. doi:10.1016/S0272-2712(18)30133-1.
   PubMed Web of Science ®Google Scholar
• Geddis AE. Congenital amegakaryocytic thrombocytopenia and thrombocytopenia with absent radii. Hematol Oncol Clin North Am 2009;23(2):321–331. doi:10.1016/j.hoc.2009.01.012.
   PubMed Web of Science ®Google Scholar
• Christensen RD, Henry E, Wiedmeier SE, Stoddard RA, Sola-Visner MC, Lambert DK, Kiehn TI, Ainsworth S. Thrombocytopenia among extremely low birth weight neonates: data from a multihospital healthcare system. J Perinatol 2006;26(6):348–353. doi:10.1038/sj.jp.7211509.
   PubMed Web of Science ®Google Scholar
• Sola-Visner MC, Christensen RD, Hutson AD, Rimsza LM. Megakaryocyte size and concentration in the bone marrow of thrombocytopenic and nonthrombocytopenic neonates. Pediatr Res 2007;61(4):479–484. doi:10.1203/pdr.0b013e3180332c18.
   PubMed Web of Science ®Google Scholar
• Ignatz M, Sola-Visner M, Rimsza LM, Fuchs D, Shuster JJ, Li X-M, Jotwani A, Staba S, Wingard JR, Hu Z, et al. Umbilical cord blood produces small megakaryocytes after transplantation. Biol Blood Marrow Transplant 2007;13(2):145–150. doi:10.1016/j.bbmt.2006.10.032.
   PubMed Web of Science ®Google Scholar
• Moore MA, Metcalf D. Ontogeny of the haemopoietic system: yolk sac origin of in vivo and in vitro colony forming cells in the developing mouse embryo. Br J Haematol 1970;18(3):279–296. doi:10.1111/j.1365-2141.1970.tb01443.x.
   PubMed Web of Science ®Google Scholar
• Fukuda T. Fetal hemopoiesis. II. Electron microscopic studies on human hepatic hemopoiesis. Virchows Arch B Cell Pathol 1974;16(3):249–270. doi:10.1007/BF02894080.
   PubMedGoogle Scholar
• Yoffey JM. The stem cell problem in the fetus. Isr J Med Sci 1971;7(7)825–833.
   PubMedGoogle Scholar
• Migliaccio G, Migliaccio AR, Petti S, Mavilio F, Russo G, Lazzaro D, Testa U, Marinucci M, Peschle C. Human embryonic hemopoiesis. Kinetics of progenitors and precursors underlying the yolk sac—-liver transition. J Clin Invest 1986;78(1):51–60. doi:10.1172/JCI112572.
   PubMed Web of Science ®Google Scholar
• Bleyer WA, Hakami N, Shepard TH. The development of hemostasis in the human fetus and newborn infant. J Pediatr 1971;79(5):838–853. doi:10.1016/S0022-3476(71)80405-5.
   PubMed Web of Science ®Google Scholar
• Enzan H, Takahashi H, Kawakami M, Yamashita S, Ohkita T, Yamamoto M. Light and electron microscopic observations of hepatic hematopoiesis of human fetuses. II. Megakaryocytopoiesis. Acta Pathol Jpn 1980;30(6):937–954. doi:10.1111/j.1440-1827.1980.tb03282.x.
   PubMedGoogle Scholar
• Daimon T, David H. An automatic image analysis of megakaryocytes in fetal liver and adult bone marrow. Z Mikrosk Anat Forsch 1982;96(3)454–460.
   PubMedGoogle Scholar
• Izumi T, Kawakami M, Enzan H, Ohkita T. The size of megakaryocytes in human fetal, infantile and adult hematopoiesis. Hiroshima J Med Sci 1983;32(3):257–260.
   PubMed Web of Science ®Google Scholar
• Carbonell F, Calvo W, Fliedner TM. Cellular composition of human fetal bone marrow. Histologic study in methacrylate sections. Acta Anat (Basel) 1982;113(4):371–375. doi:10.1159/000145570.
   PubMedGoogle Scholar
• Izumi T. Morphometric studies of megakaryocytes in human and rat fetal, infantile and adult hematopoiesis. I. Observations on human fetuses and blood dyscrasias. Hiroshima J Med Sci 1987;36(1)25–30.
   PubMedGoogle Scholar
• Naus GJ, Amann GR, Macpherson TA. Estimation of hepatic hematopoiesis in second and third trimester singleton gestations using flow cytometric light scatter analysis of archival autopsy tissue. Early Hum Dev 1992;30(2):101–107. doi:10.1016/0378-3782(92)90138-7.
   PubMed Web of Science ®Google Scholar
• Tober J, Koniski A, McGrath KE, Vemishetti R, Emerson R, de Mesy-bentley KKL, Waugh R, Palis J. The megakaryocyte lineage originates from hemangioblast precursors and is an integral component both of primitive and of definitive hematopoiesis. Blood 2007;109(4):1433–1441. doi:10.1182/blood-2006-06-031898.
   PubMed Web of Science ®Google Scholar
• Potts KS, Sargeant TJ, Markham JF, Shi W, Biben C, Josefsson EC, Whitehead LW, Rogers KL, Liakhovitskaia A, Smyth GK, et al. A lineage of diploid platelet-forming cells precedes polyploid megakaryocyte formation in the mouse embryo. Blood 2014;124(17):2725–2729. doi:10.1182/blood-2014-02-559468.
   PubMed Web of Science ®Google Scholar
• Potts KS, Sargeant TJ, Dawson CA, Josefsson EC, Hilton DJ, Alexander WS, Taoudi S. Mouse prenatal platelet-forming lineages share a core transcriptional program but divergent dependence on MPL. Blood 2015;126(6):807–816. doi:10.1182/blood-2014-12-616607.
   PubMed Web of Science ®Google Scholar
• Liu Z-J, Hoffmeister KM, Hu Z, Mager DE, Ait-Oudhia S, Debrincat MA, Pleines I, Josefsson EC, Kile BT, Italiano J, et al. Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan. Blood 2014;123(22):3381–3389. doi:10.1182/blood-2013-06-508200.
   PubMed Web of Science ®Google Scholar
• Mikkola HK, Orkin SH. The journey of developing hematopoietic stem cells. Development 2006;133(19):3733–3744. doi:10.1242/dev.02568.
   PubMed Web of Science ®Google Scholar
• Notta F, Zandi S, Takayama N, Dobson S, Gan OI, Wilson G, Kaufmann KB, McLeod J, Laurenti E, Dunant CF, et al. Distinct routes of lineage development reshape the human blood hierarchy across ontogeny. Science 2016;351(6269):aab2116. doi:10.1126/science.aab2116.
   PubMed Web of Science ®Google Scholar
• Yamamoto R, Morita Y, Ooehara J, Hamanaka S, Onodera M, Rudolph K, Ema H, Nakauchi H. Clonal analysis unveils self-renewing lineage-restricted progenitors generated directly from hematopoietic stem cells. Cell 2013;154(5):1112–1126. doi:10.1016/j.cell.2013.08.007.
   PubMed Web of Science ®Google Scholar
• Sanjuan-Pla A, Macaulay IC, Jensen CT, Woll PS, Luis TC, Mead A, Moore S, Carella C, Matsuoka S, Jones TB, et al. Platelet-biased stem cells reside at the apex of the haematopoietic stem-cell hierarchy. Nature 2013;502(7470):232–236. doi:10.1038/nature12495.
   PubMed Web of Science ®Google Scholar
• Popescu D-M, Botting RA, Stephenson E, Green K, Webb S, Jardine L, Calderbank EF, Polanski K, Goh I, Efremova M, et al. Decoding human fetal liver haematopoiesis. Nature 2019;574(7778):365–371. doi:10.1038/s41586-019-1652-y.
   PubMed Web of Science ®Google Scholar
• Olson TA, Levine RF, Mazur EM, Wright DG, Salvado AJ. Megakaryocytes and megakaryocyte progenitors in human cord blood. Am J Pediatr Hematol Oncol 1992;14(3):241–247. doi:10.1097/00043426-199208000-00011.
   PubMedGoogle Scholar
• Zauli G, Vitale L, Brunelli MA, Bagnara GP. Prevalence of the primitive megakaryocyte progenitors (BFU-meg) in adult human peripheral blood. Exp Hematol 1992;20(7):850–854.
   PubMed Web of Science ®Google Scholar
• Bruno E, Murray LJ, DiGiusto R, Mandich D, Tsukamoto A, Hoffman R. Detection of a primitive megakaryocyte progenitor cell in human fetal bone marrow. Exp Hematol 1996;24(4):552–558.
   PubMed Web of Science ®Google Scholar
• Nishihira H, Toyoda Y, Miyazaki H, Kigasawa H, Ohsaki E. Growth of macroscopic human megakaryocyte colonies from cord blood in culture with recombinant human thrombopoietin (c-mpl ligand) and the effects of gestational age on frequency of colonies. Br J Haematol 1996;92(1):23–28. doi:10.1046/j.1365-2141.1996.00287.x.
   PubMed Web of Science ®Google Scholar
• Liu Z-J, Italiano J, Ferrer-Marin F, Gutti R, Bailey M, Poterjoy B, Rimsza L, Sola-Visner M. Developmental differences in megakaryocytopoiesis are associated with up-regulated TPO signaling through mTOR and elevated GATA-1 levels in neonatal megakaryocytes. Blood 2011;117(15):4106–4117. doi:10.1182/blood-2010-07-293092.
   PubMed Web of Science ®Google Scholar
• Murray NA, Roberts IA. Circulating megakaryocytes and their progenitors (BFU-MK and CFU-MK) in term and pre-term neonates. Br J Haematol 1995;89(1):41–46. doi:10.1111/j.1365-2141.1995.tb08913.x.
   PubMed Web of Science ®Google Scholar
• Saxonhouse MA, Christensen RD, Walker DM, Hutson AD, Sola MC. The concentration of circulating megakaryocyte progenitors in preterm neonates is a function of post-conceptional age. Early Hum Dev 2004;78(2):119–124. doi:10.1016/j.earlhumdev.2004.03.009.
   PubMed Web of Science ®Google Scholar
• Woo AJ, Wieland K, Huang H, Akie TE, Piers T, Kim J, Cantor AB. Developmental differences in IFN signaling affect GATA1s-induced megakaryocyte hyperproliferation. J Clin Invest 2013;123(8):3292–3304. doi:10.1172/JCI40609.
   PubMed Web of Science ®Google Scholar
• Elagib KE, Lu C-H, Mosoyan G, Khalil S, Zasadzińska E, Foltz DR, Balogh P, Gru AA, Fuchs DA, Rimsza LM, et al. Neonatal expression of RNA-binding protein IGF2BP3 regulates the human fetal-adult megakaryocyte transition. J Clin Invest 2017;127(6):2365–2377. doi:10.1172/JCI88936.
   PubMed Web of Science ®Google Scholar
• Psaila B, Barkas N, Iskander D, Roy A, Anderson S, Ashley N, Caputo VS, Lichtenberg J, Loaiza S, Bodine DM, et al. Single-cell profiling of human megakaryocyte-erythroid progenitors identifies distinct megakaryocyte and erythroid differentiation pathways. Genome Biol 2016;17(1):83. doi:10.1186/s13059-016-0939-7.
   PubMedGoogle Scholar
• Levine RF, Olson TA, Shoff PK, Miller MK, Weisman LE. Mature micromegakaryocytes: an unusual developmental pattern in term infants. Br J Haematol 1996;94(2):391–399. doi:10.1046/j.1365-2141.1996.00666.x.
   PubMed Web of Science ®Google Scholar
• Hegyi E, Nakazawa M, Debili N, Navarro S, Katz A, Breton-Gorius J, Vainchenker W. Developmental changes in human megakaryocyte ploidy. Exp Hematol 1991;19(2):87–94.
   PubMed Web of Science ®Google Scholar
• Ma DC, Sun YH, Chang KZ, Zuo W. Developmental change of megakaryocyte maturation and DNA ploidy in human fetus. Eur J Haematol 1996;57(2):121–127. doi:10.1111/j.1600-0609.1996.tb01349.x.
   PubMed Web of Science ®Google Scholar
• Mattia G, Vulcano F, Milazzo L, Barca A, Macioce G, Giampaolo A, Hassan HJ. Different ploidy levels of megakaryocytes generated from peripheral or cord blood CD34+ cells are correlated with different levels of platelet release. Blood 2002;99(3):888–897. doi:10.1182/blood.V99.3.888.
   PubMed Web of Science ®Google Scholar
• Fuchs DA, McGinn SG, Cantu CL, Klein RR, Sola-Visner MC, Rimsza LM. Developmental differences in megakaryocyte size in infants and children. Am J Clin Pathol 2012;138(1):140–145. doi:10.1309/AJCP4EMTJYA0VGYE.
   PubMed Web of Science ®Google Scholar
• Slayton WB, Wainman DA, Li XM, Hu Z, Jotwani A, Cogle CR, Walker D, Fisher RC, Wingard JR, Scott EW, et al. Developmental differences in megakaryocyte maturation are determined by the microenvironment. Stem Cells 2005;23(9):1400–1408. doi:10.1634/stemcells.2004-0373.
   PubMed Web of Science ®Google Scholar
• Pastos KM, Slayton WB, Rimsza LM, Young L, Sola-Visner MC. Differential effects of recombinant thrombopoietin and bone marrow stromal-conditioned media on neonatal versus adult megakaryocytes. Blood 2006;108(10):3360–3362. doi:10.1182/blood-2006-04-018036.
   PubMed Web of Science ®Google Scholar
• Klusmann J-H, Godinho FJ, Heitmann K, Maroz A, Lee Koch M, Reinhardt D, Orkin SH, Li Z. Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis. Genes Dev 2010;24(15):1659–1672. doi:10.1101/gad.1903410.
   PubMed Web of Science ®Google Scholar
• Zhang CC, Lodish HF. Insulin-like growth factor 2 expressed in a novel fetal liver cell population is a growth factor for hematopoietic stem cells. Blood 2004;103(7):2513–2521. doi:10.1182/blood-2003-08-2955.
   PubMed Web of Science ®Google Scholar
• Chou S, Lodish HF. Fetal liver hepatic progenitors are supportive stromal cells for hematopoietic stem cells. Proc Natl Acad Sci U S A 2010;107(17):7799–7804. doi:10.1073/pnas.1003586107.
   PubMed Web of Science ®Google Scholar
• Sugiyama D, Kulkeaw K, Mizuochi C. TGF-beta-1 up-regulates extra-cellular matrix production in mouse hepatoblasts. Mech Dev 2013;130(2–3):195–206. doi:10.1016/j.mod.2012.09.003.
   PubMed Web of Science ®Google Scholar
• Thompson NL, Flanders KC, Smith JM, Ellingsworth LR, Roberts AB, Sporn MB. Expression of transforming growth factor-beta 1 in specific cells and tissues of adult and neonatal mice. J Cell Biol 1989;108(2):661–669. doi:10.1083/jcb.108.2.661.
   PubMed Web of Science ®Google Scholar
• Bluteau O, Langlois T, Rivera-Munoz P, Favale F, Rameau P, Meurice G, Dessen P, Solary E, Raslova H, Mercher T, et al. Developmental changes in human megakaryopoiesis. J Thromb Haemost 2013;11(9):1730–1741. doi:10.1111/jth.12326.
   PubMed Web of Science ®Google Scholar
• Ferrer-Marin F, Gutti R, Liu Z-J, Sola-Visner M. MiR-9 contributes to the developmental differences in CXCR-4 expression in human megakaryocytes. J Thromb Haemost 2014;12(2):282–285. doi:10.1111/jth.12469.
   Web of Science ®Google Scholar
• Mazharian A, Watson SP, Severin S. Critical role for ERK1/2 in bone marrow and fetal liver-derived primary megakaryocyte differentiation, motility, and proplatelet formation. Exp Hematol 2009;37(10):1238–1249 e5. doi:10.1016/j.exphem.2009.07.006.
   PubMed Web of Science ®Google Scholar
• Avecilla ST, Hattori K, Heissig B, Tejada R, Liao F, Shido K, Jin DK, Dias S, Zhang F, Hartman TE, et al. Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nat Med 2004;10(1):64–71. doi:10.1038/nm973.
   PubMed Web of Science ®Google Scholar
• Kandi R, Gutti U, Undi R, Sahu I, Gutti RK. Understanding thrombocytopenia: physiological role of microRNA in survival of neonatal megakaryocytes. J Thromb Thrombolysis 2015;40(3):310–316. doi:10.1007/s11239-015-1238-y.
   PubMed Web of Science ®Google Scholar
• Li X, Zhang J, Gao L, McClellan S, Finan MA, Butler TW, Owen LB, Piazza GA, Xi Y. MiR-181 mediates cell differentiation by interrupting the Lin28 and let-7 feedback circuit. Cell Death Differ 2012;19(3):378–386. doi:10.1038/cdd.2011.127.
   PubMed Web of Science ®Google Scholar
• Raslova H, Baccini V, Loussaief L, Comba B, Larghero J, Debili N, Vainchenker W. Mammalian target of rapamycin (mTOR) regulates both proliferation of megakaryocyte progenitors and late stages of megakaryocyte differentiation. Blood 2006;107(6):2303–2310. doi:10.1182/blood-2005-07-3005.
   PubMed Web of Science ®Google Scholar
• Elagib KE, Rubinstein J, Delehanty L, Ngoh V, Greer P, Li S, Lee J, Li Z, Orkin S, Mihaylov I, et al. Calpain 2 activation of P-TEFb drives megakaryocyte morphogenesis and is disrupted by leukemogenic GATA1 mutation. Dev Cell 2013;27(6):607–620. doi:10.1016/j.devcel.2013.11.013.
   PubMed Web of Science ®Google Scholar
• Elagib KE, Goldfarb AN. Megakaryocytic irreversible P-TEFb activation. Cell Cycle 2014;13(12):1827–1828. doi:10.4161/cc.29324.
   PubMed Web of Science ®Google Scholar
• Andrew M, Castle V, Saigal S, Carter C, Kelton JG. Clinical impact of neonatal thrombocytopenia. J Pediatr 1987;110(3):457–464. doi:10.1016/S0022-3476(87)80517-6.
   PubMed Web of Science ®Google Scholar
• Castle V, Andrew M, Kelton J, Giron D, Johnston M, Carter C. Frequency and mechanism of neonatal thrombocytopenia. J Pediatr 1986;108(5 Pt 1):749–755. doi:10.1016/S0022-3476(86)81059-9.
   PubMed Web of Science ®Google Scholar
• Harker LA. Kinetics of thrombopoiesis. J Clin Invest 1968;47(3):458–465. doi:10.1172/JCI105742.
   PubMed Web of Science ®Google Scholar
• Harker LA, Finch CA. Thrombokinetics in man. J Clin Invest 1969;48(6):963–974. doi:10.1172/JCI106077.
   PubMed Web of Science ®Google Scholar
• Hu Z, Slayton WB, Rimsza LM, Bailey M, Sallmon H, Sola-Visner MC. Differences between newborn and adult mice in their response to immune thrombocytopenia. Neonatology 2010;98(1):100–108. doi:10.1159/000280413.
   PubMed Web of Science ®Google Scholar
• Sparger KA, Ramsey H, Lorenz V, Liu ZJ, Feldman HA, Laforest T, Sola-Visner MC. Developmental differences between newborn and adult mice in response to romiplostim. Platelets 2018 Jun;29(4):365–372. doi:10.1080/09537104.2017.1316481.
   PubMed Web of Science ®Google Scholar
• Laughlin MJ, Eapen M, Rubinstein P, Wagner JE, Zhang M-J, Champlin RE, Stevens C, Barker JN, Gale RP, Lazarus HM, et al. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med 2004;351(22):2265–2275. doi:10.1056/NEJMoa041276.
   PubMed Web of Science ®Google Scholar
• Gurbuxani S, Vyas P, Crispino JD. Recent insights into the mechanisms of myeloid leukemogenesis in Down syndrome. Blood 2004;103(2):399–406. doi:10.1182/blood-2003-05-1556.
   PubMed Web of Science ®Google Scholar
• Mateos MK, Barbaric D, Byatt S-A, Sutton R, Marshall GM. Down syndrome and leukemia: insights into leukemogenesis and translational targets. Transl Pediatr 2015;4(2):76–92. doi:10.3978/j..2224-4336.2015.03.03.
   PubMed Web of Science ®Google Scholar
• Roy A, Roberts I, Norton A, Vyas P. Acute megakaryoblastic leukaemia (AMKL) and transient myeloproliferative disorder (TMD) in Down syndrome: a multi-step model of myeloid leukaemogenesis. Br J Haematol 2009;147(1):3–12. doi:10.1111/bjh.2009.147.issue-1.
   PubMed Web of Science ®Google Scholar
• Tunstall-Pedoe O, Roy A, Karadimitris A, de la Fuente J, Fisk NM, Bennett P, Norton A, Vyas P, Roberts I. Abnormalities in the myeloid progenitor compartment in Down syndrome fetal liver precede acquisition of GATA1 mutations. Blood 2008;112(12):4507–4511. doi:10.1182/blood-2008-04-152967.
   PubMed Web of Science ®Google Scholar
• Calligaris R, Bottardi S, Cogoi S, Apezteguia I, Santoro C. Alternative translation initiation site usage results in two functionally distinct forms of the GATA-1 transcription factor. Proc Natl Acad Sci U S A 1995;92(25):11598–11602. doi:10.1073/pnas.92.25.11598.
   PubMed Web of Science ®Google Scholar
• Vainchenker W, Kieffer N. Human megakaryocytopoiesis: in vitro regulation and characterization of megakaryocytic precursor cells by differentiation markers. Blood Rev 1988;2(2):102–107. doi:10.1016/0268-960X(88)90031-8.
   PubMed Web of Science ®Google Scholar
• Hitzler JK, Cheung J, Li Y, Scherer SW, Zipursky A. GATA1 mutations in transient leukemia and acute megakaryoblastic leukemia of Down syndrome. Blood 2003;101(11):4301–4304. doi:10.1182/blood-2003-01-0013.
   PubMed Web of Science ®Google Scholar
• Yoshida K, Toki T, Okuno Y, Kanezaki R, Shiraishi Y, Sato-Otsubo A, Sanada M, Park M-J, Terui K, Suzuki H. The landscape of somatic mutations in Down syndrome-related myeloid disorders. Nat Genet 2013;45(11):1293–1299. doi:10.1038/ng.2759.
   PubMed Web of Science ®Google Scholar
• King S, Germeshausen M, Strauss G, Welte K, Ballmaier M. Congenital amegakaryocytic thrombocytopenia: a retrospective clinical analysis of 20 patients. Br J Haematol 2005;131(5):636–644. doi:10.1111/bjh.2005.131.issue-5.
   PubMed Web of Science ®Google Scholar
• Germeshausen M, Ballmaier M, Welte K. MPL mutations in 23 patients suffering from congenital amegakaryocytic thrombocytopenia: the type of mutation predicts the course of the disease. Hum Mutat 2006;27(3):296. doi:10.1002/()1098-1004.
   PubMedGoogle Scholar
• Fox NE, Chen R, Hitchcock I, Keates-Baleeiro J, Frangoul H, Geddis AE. Compound heterozygous c-Mpl mutations in a child with congenital amegakaryocytic thrombocytopenia: functional characterization and a review of the literature. Exp Hematol 2009;37(4):495–503. doi:10.1016/j.exphem.2009.01.001.
   PubMed Web of Science ®Google Scholar
• Rose MJ, Nicol KK, Skeens MA, Gross TG, Kerlin BA. Congenital amegakaryocytic thrombocytopenia: the diagnostic importance of combining pathology with molecular genetics. Pediatr Blood Cancer 2008;50(6):1263–1265. doi:10.1002/()1545-5017.
   PubMed Web of Science ®Google Scholar
• Henter JI, Winiarski J, Ljungman P, Ringdén O, Ost A. Bone marrow transplantation in two children with congenital amegakaryocytic thrombocytopenia. Bone Marrow Transplant 1995;15(5):799–801.
   PubMed Web of Science ®Google Scholar
• Lorenz V, Ramsey H, Liu Z-J, Italiano J, Hoffmeister K, Bihorel S, Mager D, Hu Z, Slayton W, Kile B, et al. Developmental stage-specific manifestations of absent TPO/c-MPL signalling in newborn mice. Thromb Haemost 2017;117(12):2322–2333. doi:10.1160/TH17-06-0433.
   PubMed Web of Science ®Google Scholar
• Fiedler J, Strauss G, Wannack M, Schwiebert S, Seidel K, Henning K, Klopocki E, Schmugge M, Gaedicke G, Schulze H, et al. Two patterns of thrombopoietin signaling suggest no coupling between platelet production and thrombopoietin reactivity in thrombocytopenia-absent radii syndrome. Haematologica 2012;97(1):73–81. doi:10.3324/haematol.2011.049619.
   PubMed Web of Science ®Google Scholar
• Klopocki E, Schulze H, Strauß G, Ott C-E, Hall J, Trotier F, Fleischhauer S, Greenhalgh L, Newbury-Ecob RA, Neumann LM, et al. Complex inheritance pattern resembling autosomal recessive inheritance involving a microdeletion in thrombocytopenia-absent radius syndrome. Am J Hum Genet 2007;80(2):232–240. doi:10.1086/510919.
   PubMed Web of Science ®Google Scholar
• Albers CA, Newbury-Ecob R, Ouwehand WH, Ghevaert C. New insights into the genetic basis of TAR (thrombocytopenia-absent radii) syndrome. Curr Opin Genet Dev 2013;23(3):316–323. doi:10.1016/j.gde.2013.02.015.
   PubMed Web of Science ®Google Scholar