Summary: The process of generating white blood cells (LEUKOCYTES) from the pluripotent HEMATOPOIETIC STEM CELLS of the BONE MARROW. There are two significant pathways to generate various types of leukocytes: MYELOPOIESIS, in which leukocytes in the blood are derived from MYELOID STEM CELLS, and LYMPHOPOIESIS, in which leukocytes of the lymphatic system (LYMPHOCYTES) are generated from lymphoid stem cells.

Top Publications

  1. Hochedlinger K, Jaenisch R. Monoclonal mice generated by nuclear transfer from mature B and T donor cells. Nature. 2002;415:1035-8 pubmed
    ..Similarly, a mouse cloned from a T-cell nucleus carried rearranged T-cell-receptor genes in all tissues. This is an unequivocal demonstration that a terminally differentiated cell can be reprogrammed to produce an adult cloned animal. ..
  2. Hogan M, Weissman D, Hubbs A, Gibson L, Piktel D, Landreth K. Regulation of eosinophilopoiesis in a murine model of asthma. J Immunol. 2003;171:2644-51 pubmed
    ..Differentiation of eosinophil progenitor cells and phenotypic eosinophilia is T cell dependent and does not occur in athymic nude mice exposed to intranasal allergen. ..
  3. Zivny J, Jelinek J, Pospisilova D, Plasilova M, Necas E, Stopka T. Diamond blackfan anemia stem cells fail to repopulate erythropoiesis in NOD/SCID mice. Blood Cells Mol Dis. 2003;31:93-7 pubmed
    ..Therefore, we conclude that disordered DBA erythropoiesis may be a result of defective erythroid-lineage commitment and maintenance of early erythroid progenitors. ..
  4. Cotta C, Zhang Z, Kim H, Klug C. Pax5 determines B- versus T-cell fate and does not block early myeloid-lineage development. Blood. 2003;101:4342-6 pubmed
    ..These results implicate Pax5 as a critical regulator of B- versus T-cell developmental fate and suggest that Pax5 may promote commitment to the B-cell lineage by mechanisms that are independent of myeloid gene repression. ..
  5. Dugan A, Thellin O, Buckley D, Buckley A, Ogle C, Horseman N. Effects of prolactin deficiency on myelopoiesis and splenic T lymphocyte proliferation in thermally injured mice. Endocrinology. 2002;143:4147-51 pubmed
    ..This study supports the hypothesis that the immunomodulatory effects of PRL are manifest when the organism is subjected to stress. ..
  6. Basu S, Hodgson G, Zhang H, Katz M, Quilici C, Dunn A. "Emergency" granulopoiesis in G-CSF-deficient mice in response to Candida albicans infection. Blood. 2000;95:3725-33 pubmed
    ..Blood. 2000;95:3725-3733) ..
  7. Nagata K, Nakamura T, Kitamura F, Kuramochi S, Taki S, Campbell K, et al. The Ig alpha/Igbeta heterodimer on mu-negative proB cells is competent for transducing signals to induce early B cell differentiation. Immunity. 1997;7:559-70 pubmed
    ..Thus, the cross-linking of Ig beta on proB cells appears to elicit differentiation signals analogous to those delivered by the preB cell receptor in normal B cell development. ..
  8. Basu S, Hodgson G, Katz M, Dunn A. Evaluation of role of G-CSF in the production, survival, and release of neutrophils from bone marrow into circulation. Blood. 2002;100:854-61 pubmed
    ..Collectively, our data suggest that at steady state, G-CSF is critical for the survival of granulocytic cells; however, it is dispensable for trafficking of granulocytes from bone marrow into circulation. ..
  9. Grignani F, Valtieri M, Gabbianelli M, Gelmetti V, Botta R, Luchetti L, et al. PML/RAR alpha fusion protein expression in normal human hematopoietic progenitors dictates myeloid commitment and the promyelocytic phenotype. Blood. 2000;96:1531-7 pubmed
    ..Blood. 2000;96:1531-1537) ..

More Information


  1. Lin M, Sakamoto K. p55Cdc/cdc20 overexpression promotes early g1/s transition in myeloid cells. Stem Cells. 2001;19:205-11 pubmed
    ..Cyclin B1 levels were lower at early G1 phase in cells overexpressing p55Cdc/Cdc20. Our results suggest that p55Cdc/Cdc20 may play an important role in G1 to S transition during myelopoiesis. ..
  2. McCune J. The dynamics of CD4+ T-cell depletion in HIV disease. Nature. 2001;410:974-9 pubmed
    ..Ironically, this failure may be precipitated by physiological mechanisms designed to maintain homeostasis in the face of accelerated T-cell loss. ..
  3. Ancliff P, Gale R, Watts M, Liesner R, Hann I, Strobel S, et al. Paternal mosaicism proves the pathogenic nature of mutations in neutrophil elastase in severe congenital neutropenia. Blood. 2002;100:707-9 pubmed
    ..This is the first in vivo confirmation of the pathogenic nature of elastase mutations in humans. The normal neutrophil count in the father suggests that the mutant elastase does not have paracrine effects. ..
  4. Dileepan K, Johnston T, Li Y, Tawfik O, Stechschulte D. Deranged aortic intima-media thickness, plasma triglycerides and granulopoiesis in Sl/Sl(d) mice. Mediators Inflamm. 2004;13:335-41 pubmed
    ..Interestingly, the high-fat diet regimen elevated leukocyte counts and the number of monocytes and granulocytes in Sl/Sl(d) mice. ..
  5. Reya T, O RIORDAN M, Okamura R, Devaney E, Willert K, Nusse R, et al. Wnt signaling regulates B lymphocyte proliferation through a LEF-1 dependent mechanism. Immunity. 2000;13:15-24 pubmed
    ..Finally, we establish a link between Wnt signaling and normal B cell development by demonstrating that Wnt proteins are mitogenic for pro-B cells and that this effect is mediated by LEF-1. ..
  6. Nerlov C, Querfurth E, Kulessa H, Graf T. GATA-1 interacts with the myeloid PU.1 transcription factor and represses PU.1-dependent transcription. Blood. 2000;95:2543-51 pubmed
    ..We therefore propose that GATA-1 represses myeloid gene expression, at least in part, through its ability to directly interact with the PU.1 ETS domain and thereby interfere with PU.1 function. (Blood. 2000;95:2543-2551) ..
  7. Katzerke C, Madan V, Gerloff D, Bräuer Hartmann D, Hartmann J, Wurm A, et al. Transcription factor C/EBP?-induced microRNA-30c inactivates Notch1 during granulopoiesis and is downregulated in acute myeloid leukemia. Blood. 2013;122:2433-42 pubmed publisher
    ..These data reveal the importance of deregulated miRNA expression in leukemia and may provide novel biomarkers and therapeutic targets in AML. ..
  8. Silvestris N, Del Re M, Azzariti A, Maiello E, Lombardi L, Cinieri S, et al. Optimized granulocyte colony-stimulating factor prophylaxis in adult cancer patients: from biological principles to clinical guidelines. Expert Opin Ther Targets. 2012;16 Suppl 2:S111-7 pubmed publisher
    ..In the interim, physicians should remember that small differences in biochemical and biophysical characteristics might translate into differences in potency and immunogenic potential. ..
  9. Werlen G, Hausmann B, Palmer E. A motif in the alphabeta T-cell receptor controls positive selection by modulating ERK activity. Nature. 2000;406:422-6 pubmed
    ..Therefore, an intact DIG-associated signalosome is essential for sustained ERK activation, which leads to positive selection. ..
  10. Ruedl C, Bachmann M, Kopf M. The antigen dose determines T helper subset development by regulation of CD40 ligand. Eur J Immunol. 2000;30:2056-64 pubmed
    ..Thus, we propose that (1) peptide-MHC density and (2) accessory molecules such as LFA-1 determine T helper polarization by regulation of CD40L. ..
  11. Roberts P, Mollapour E, Watts M, Linch D. Primitive myeloid cells express high levels of phospholipase A(2) activity in the absence of leukotriene release: selective regulation by stem cell factor involving the MAP kinase pathway. Blood. 1999;94:1261-72 pubmed
    ..These data provide the first evidence that primitive myeloid cells have the capacity to release arachidonate, which is regulated by an early acting hematopoietic growth factor important for the growth and survival of these cells. ..
  12. Tamura T, Nagamura Inoue T, Shmeltzer Z, Kuwata T, Ozato K. ICSBP directs bipotential myeloid progenitor cells to differentiate into mature macrophages. Immunity. 2000;13:155-65 pubmed
    ..Together, ICSBP has a key role in the myeloid cell lineage selection and macrophage maturation. ..
  13. Germeshausen M, Skokowa J, Ballmaier M, Zeidler C, Welte K. G-CSF receptor mutations in patients with congenital neutropenia. Curr Opin Hematol. 2008;15:332-7 pubmed publisher
    ..Congenital neutropenia patients with acquired CSF3R mutations define a group with high risk for development of leukemia. ..
  14. Curtis D, Jane S, Hilton D, Dougherty L, Bodine D, Begley C. Adaptor protein SKAP55R is associated with myeloid differentiation and growth arrest. Exp Hematol. 2000;28:1250-9 pubmed
    ..In contrast, a tyrosine 260 mutant mSKAP55R had no effect on in vitro growth. These studies implicate mSKAP55R in the processes of myeloid differentiation and growth arrest. ..
  15. Justo G, Silva M, Queiroz M. Effects of the green algae Chlorella vulgaris on the response of the host hematopoietic system to intraperitoneal ehrlich ascites tumor transplantation in mice. Immunopharmacol Immunotoxicol. 2001;23:119-32 pubmed
    ..These results suggest a protective antitumor effect of CVE which might be attributable, at least in part, to the stimulation of the production and, possibly, maturation of granulocytes and macrophages. ..
  16. Dunon D, Allioli N, Vainio O, Ody C, Imhof B. Renewal of thymocyte progenitors and emigration of thymocytes during avian development. Dev Comp Immunol. 1998;22:279-87 pubmed
    ..Finally, analysis of thymocyte differentiation suggested that gamma delta and alpha beta T cells migrate from the thymus to the periphery in alternating waves. ..
  17. Kerre T, De Smet G, De Smedt M, Zippelius A, Pittet M, Langerak A, et al. Adapted NOD/SCID model supports development of phenotypically and functionally mature T cells from human umbilical cord blood CD34(+) cells. Blood. 2002;99:1620-6 pubmed
    ..In approximately half of these mice, the peripheral T cells included a pauciclonal outgrowth of CD45RO(+) cells. These data suggest that all elements of a functional immune system were present in these animals. ..
  18. Mebius R, Rennert P, Weissman I. Developing lymph nodes collect CD4+CD3- LTbeta+ cells that can differentiate to APC, NK cells, and follicular cells but not T or B cells. Immunity. 1997;7:493-504 pubmed
    ..Since the necessity of lymphotoxin in lymphoid organ development has been shown, we propose that the novel subset of CD4+CD3-LTbeta+ fetal cells is instrumental in the development of lymphoid tissue architecture. ..
  19. Kreisel D, Sugimoto S, Zhu J, Nava R, Li W, Okazaki M, et al. Emergency granulopoiesis promotes neutrophil-dendritic cell encounters that prevent mouse lung allograft acceptance. Blood. 2011;118:6172-82 pubmed publisher
    ..Our findings identify granulopoiesis-mediated augmentation of alloimmunity as a novel link between innate and adaptive immune responses after organ transplantation. ..
  20. Matzer S, Baumann T, Lukacs N, Rollinghoff M, Beuscher H. Constitutive expression of macrophage-inflammatory protein 2 (MIP-2) mRNA in bone marrow gives rise to peripheral neutrophils with preformed MIP-2 protein. J Immunol. 2001;167:4635-43 pubmed
    ..Together, the data imply a constitutive production of MIP-2 by a subset of PMNs in BM and argue for the possibility of a rapid mobilization of MIP-2 through its storage in circulating PMNs. ..
  21. Khanna Gupta A, Zibello T, Sun H, Lekstrom Himes J, Berliner N. C/EBP epsilon mediates myeloid differentiation and is regulated by the CCAAT displacement protein (CDP/cut). Proc Natl Acad Sci U S A. 2001;98:8000-5 pubmed
    ..We further demonstrate that the C/EBP epsilon promoter is regulated by CDP/cut during myeloid differentiation. ..
  22. Kreisel D, Sugimoto S, Tietjens J, Zhu J, Yamamoto S, Krupnick A, et al. Bcl3 prevents acute inflammatory lung injury in mice by restraining emergency granulopoiesis. J Clin Invest. 2011;121:265-76 pubmed publisher
    ..These data demonstrate a critical role for Bcl3 in regulating emergency granulopoiesis and suggest that targeting the differentiation of myeloid progenitors may be a therapeutic strategy for preventing inflammatory lung injury. ..
  23. Fuller J, McAdara J, Yaron Y, Sakaguchi M, Fraser J, Gasson J. Characterization of HOX gene expression during myelopoiesis: role of HOX A5 in lineage commitment and maturation. Blood. 1999;93:3391-400 pubmed
    ..Also, overexpression of HOX A5 inhibited erythroid differentiation of the K562 cell line. Based on these observations, we propose that HOX A5 functions as an important regulator of hematopoietic lineage determination and maturation. ..
  24. Hing J, Perez Ruixo J, Stuyckens K, Soto Matos A, Lopez Lazaro L, Zannikos P. Mechanism-based pharmacokinetic/pharmacodynamic meta-analysis of trabectedin (ET-743, Yondelis) induced neutropenia. Clin Pharmacol Ther. 2008;83:130-43 pubmed
    ..The extent and time course of neutropenia following six different dosing regimens of trabectedin were well predicted by the semiphysiological PK/PD model. ..
  25. Kumagai T, Morimoto K, Saitoh T, Tsuboi I, Aikawa S, Horie T. Age-related changes in myelopoietic response to lipopolysaccharide in senescence-accelerated (SAM) mice. Mech Ageing Dev. 2000;112:153-67 pubmed
    ..These imbalances in the regulatory factors derived from non-hemopoietic cells in the bones may lead to an inappropriate response of myelopoiesis in aged SAM mice after LPS administration, which may play a key role in infections. ..
  26. Esposito R, Durante M, Gialanella G, Grossi G, Pugliese M, Scampoli P, et al. A model of radiation-induced myelopoiesis in space. Phys Med. 2001;17 Suppl 1:181-2 pubmed
    ..A dedicated computer code was written and applied to solar particle events and to the mission to Mars. The results suggest that altered myelopoiesis and lymphopoiesis in microgravity might increase human radiosensitivity in space. ..
  27. Nasirikenari M, Segal B, Ostberg J, Urbasic A, Lau J. Altered granulopoietic profile and exaggerated acute neutrophilic inflammation in mice with targeted deficiency in the sialyltransferase ST6Gal I. Blood. 2006;108:3397-405 pubmed
    ..Together, our study demonstrated a role for ST6Gal-1, possibly from extramedullary sources (eg, produced in liver) in regulating inflammation, circulating neutrophil homeostasis, and replenishing granulocyte numbers. ..
  28. Rodriguez Perales S, Cano F, Lobato M, Rabbitts T. MLL gene fusions in human leukaemias: in vivo modelling to recapitulate these primary tumourigenic events. Int J Hematol. 2008;87:3-9 pubmed publisher
    ..An important finding of this work is that the lineage of the tumours can be controlled by the MLL-protein fusion. The translocation mimic methods can be applied to any human reciprocal chromosomal translocation. ..
  29. Yu J, Ruddy M, Wong G, Sfintescu C, Baker P, Smith J, et al. An essential role for IL-17 in preventing pathogen-initiated bone destruction: recruitment of neutrophils to inflamed bone requires IL-17 receptor-dependent signals. Blood. 2007;109:3794-802 pubmed
    ..These results indicate a nonredundant role for IL-17 in mediating host defense via neutrophil mobilization. ..
  30. Kallies A, Rosenbauer F, Scheller M, Knobeloch K, Horak I. Accumulation of c-Cbl and rapid termination of colony-stimulating factor 1 receptor signaling in interferon consensus sequence binding protein-deficient bone marrow-derived macrophages. Blood. 2002;99:3213-9 pubmed
    ..Congruently, the expression of a major endosomal/lysosomal protease, cathepsin B, is strongly reduced in ICSBP(-/-) BMMs. ..
  31. Baatout S. A historical perspective and cellular regulation of megakaryocytopoiesis. Haematologia (Budap). 1998;29:67-79 pubmed
    ..This review will discuss megakaryocyte ontogeny, cell-cell interactions between megakaryocytes and the other stromal cells and the signal transduction in megakaryocytes. ..
  32. Broxmeyer H, Cooper S, Hangoc G, Gao J, Murphy P. Dominant myelopoietic effector functions mediated by chemokine receptor CCR1. J Exp Med. 1999;189:1987-92 pubmed
    ..CCR1 is not a dominant receptor for MIP-1alpha suppression of MPC proliferation, but it does negatively impact G-CSF-induced MPC mobilization. ..
  33. Galm O, Fabry U, Adam G, Osieka R. Pneumatosis intestinalis following cytotoxic or immunosuppressive treatment. Digestion. 2001;64:128-32 pubmed
    ..It can be managed successfully by conservative treatment in the absence of secondary complications, if there is recovery of myelopoiesis. ..
  34. Wong E, Jenne D, Zimmer M, Porter S, Gilks C. Changes in chromatin organization at the neutrophil elastase locus associated with myeloid cell differentiation. Blood. 1999;94:3730-6 pubmed
    ..The altered chromatin structure specific to cells that actively transcribe the AZU1-PRTN3-ELA2 genes suggests that chromatin reorganization is an important mechanism regulating the myeloid-specific transcription of this gene cluster. ..
  35. Ulich T, Del Castillo J, Senaldi G, Hartley C, Molineux G. PEG-rHuMGDF promotes multilineage hematopoietic recovery in myelosuppressed mice. Exp Hematol. 1999;27:1776-81 pubmed
  36. Miyazaki T, Lemonnier F. Modulation of thymic selection by expression of an immediate-early gene, early growth response 1 (Egr-1). J Exp Med. 1998;188:715-23 pubmed
    ..These results suggest that expression of Egr-1 and/or its target gene(s) may directly influence the thresholds required for thymocyte selection. ..
  37. Kaplan I, Morisot S, Heiser D, Cheng W, Kim M, Civin C. Deletion of tristetraprolin caused spontaneous reactive granulopoiesis by a non-cell-autonomous mechanism without disturbing long-term hematopoietic stem cell quiescence. J Immunol. 2011;186:2826-34 pubmed publisher
    ..These findings demonstrate the importance of TTP in inflammatory homeostasis and highlight the ability of the hematopoietic system to respond to stress without significant numbers of quiescent HSCs entering the cell cycle. ..
  38. Taylor C, Moreira C, Murray M. A retrospective study of malaria in pediatric oncology patients in Senegal. J Pediatr Hematol Oncol. 2011;33:325-9 pubmed publisher
    ..00, P=0.28, P=0.53, and P=0.22, respectively). Despite the high incidence of myelosuppression in pediatric oncology patients, we found no evidence that this was associated with increased fatality of malaria episodes. ..
  39. Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature. 1999;401:708-12 pubmed
  40. Lutton B, Callard I. Influence of reproductive activity, sex steroids, and seasonality on epigonal organ cellular proliferation in the skate (Leucoraja erinacea). Gen Comp Endocrinol. 2008;155:116-25 pubmed
    ..These studies suggest functional interactions between reproductive and immune tissues in the skate, and that cellular turnover in epigonal tissue may be influenced by gonadal activity. ..
  41. Gur iantseva L, Zhdanov V, Udut E, Simanina E, Khrichkova T, Dygai A. [Mechanisms of action of the stimulators of granulocytopoiesis under cytostatic myelosuppression conditions]. Eksp Klin Farmakol. 2006;69:44-7 pubmed
  42. Granick J, Falahee P, Dahmubed D, Borjesson D, Miller L, Simon S. Staphylococcus aureus recognition by hematopoietic stem and progenitor cells via TLR2/MyD88/PGE2 stimulates granulopoiesis in wounds. Blood. 2013;122:1770-8 pubmed publisher
    ..We conclude that granulopoiesis in S aureus-infected wounds is induced by TLR2/MyD88 activation of HSPCs through a mechanism that involves autocrine production and activity of PGE2. ..
  43. Varnum Finney B, Xu L, Brashem Stein C, Nourigat C, Flowers D, Bakkour S, et al. Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nat Med. 2000;6:1278-81 pubmed
  44. Mostoslavsky R, Singh N, Tenzen T, Goldmit M, Gabay C, Elizur S, et al. Asynchronous replication and allelic exclusion in the immune system. Nature. 2001;414:221-5 pubmed
    ..These results indicate that allelic exclusion in the immune system may be very similar to the process of X chromosome inactivation. ..
  45. Steinman R, Huang J, Yaroslavskiy B, Goff J, Ball E, Nguyen A. Regulation of p21(WAF1) expression during normal myeloid differentiation. Blood. 1998;91:4531-42 pubmed
  46. Fang W, Weintraub B, Dunlap B, Garside P, Pape K, Jenkins M, et al. Self-reactive B lymphocytes overexpressing Bcl-xL escape negative selection and are tolerized by clonal anergy and receptor editing. Immunity. 1998;9:35-45 pubmed
    ..These studies suggest that Bcl-x may have a distinct role in controlling survival at the immature stage of B cell development and demonstrate that tolerance is preserved when self-reactive B cells escape central deletion. ..
  47. Larsen M, Häger M, Glenthøj A, Asmar F, Clemmensen S, Mora Jensen H, et al. miRNA-130a regulates C/EBP-? expression during granulopoiesis. Blood. 2014;123:1079-89 pubmed publisher
    ..We conclude that miR-130a is important for the regulation of the timed expression of C/EBP-? during granulopoiesis. ..
  48. Nemoto Y, Kanai T, Tohda S, Totsuka T, Okamoto R, Tsuchiya K, et al. Negative feedback regulation of colitogenic CD4+ T cells by increased granulopoiesis. Inflamm Bowel Dis. 2008;14:1491-503 pubmed publisher
    ..These results suggest that the increased granulopoiesis by colitogenic BM CD4(+) T cells represent a negative feedback mechanism to control systemic inflammation. ..
  49. Amrani A, Verdaguer J, Serra P, Tafuro S, Tan R, Santamaria P. Progression of autoimmune diabetes driven by avidity maturation of a T-cell population. Nature. 2000;406:739-42 pubmed
    ..We conclude that avidity maturation of pathogenic T-cell populations may be the key event in the progression of benign inflammation to overt disease in autoimmunity. ..
  50. Liebermann D, Hoffman B. Interferon regulatory factor-1 myelodysplasia and leukemia. Leuk Res. 2006;30:1069-71 pubmed
  51. Schessl C, Rawat V, Cusan M, Deshpande A, Kohl T, Rosten P, et al. The AML1-ETO fusion gene and the FLT3 length mutation collaborate in inducing acute leukemia in mice. J Clin Invest. 2005;115:2159-68 pubmed
  52. Kosak S, Skok J, Medina K, Riblet R, Le Beau M, Fisher A, et al. Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development. Science. 2002;296:158-62 pubmed
    ..We suggest that subnuclear positioning represents a novel means of regulating transcription and recombination of IgH and Igkappa loci during lymphocyte development. ..
  53. Galoyan A, Aprikyan V. A new hypothalamic polypeptide is a regulator of myelopoiesis. Neurochem Res. 2002;27:305-12 pubmed
    ..Our results may indicate the ability of PRP to stimulate recovery of myelopoiesis and enhance mature neutrophil function. ..