the attached hematopoiteic cascade

Hematopoietic Cascade
Pluripotent Stem Cell
IL-1 SCF
IL-6 Flt3L
IL-3 IL-11
TPO
Myeloid Stem Cell
GM-CSF
IL-3
Flt3L
SCF
IL-7
G-CSF
Lymphoid Stem Cell
CFU-BLAST
SCF
Flt3L
IL-1
IL-6
IL-7
Flt3L
SCF
GM-CSF
IL-11
IL-6
TPO
IL-3
Flt3L
SCF
GM-CSF
IL-3
CFU-GEMM
GM-CSF
BFU-MK
CFU-G
CFU-GM
GM-CSF
IL-3
IL-6
IL-11
TPO
SCF
Flt3L
Myeloblast
GM-CSF
G-CSF
CFU-E
CFU-MK
Neutrophilic Myelocyte
GM-CSF
G-CSF
TPO
EPO
IL-3
SCF
GM-CSF
IL-3
TPO
IL-11
IL-6
GM-CSF
IL-3
SCF
Flt3L
TNF
IL-7
Flt3L
CFU-M/DC
CFU-Eo
GM-CSF
IL-5
IL-3
GM-CSF
M-CSF
IL-3
CFU-Bas
GM-CSF
Flt3L
TNF
SCF
IL-4
GM-CSF
M-CSF
IL-3
GM-CSF
IL-5
IL-3
Eosinophilic
Myelocyte
Promonocyte
GM-CSF
M-CSF
IL-3
GM-CSF
IL-5
IL-3
E. Metamyelocyte
GM-CSF
G-CSF
EPO
TPO
IL-11
IL-6
GM-CSF
IL-5
IL-3
Monocyte
Band Neutrophil
GM-CSF
M-CSF
IFN
Band Eosinophil
GM-CSF
IL-5
IL-3
Neutrophil
© 2009 Genzyme Corporation. All rights reserved LEU/US/P023/0709 Printed in USA July 2009
Macrophage
Myeloid-related
Dendritic Cell
Eosinophil
Flt3L
IL-7
Flt3L
IL-15
CFU-Mast
NK Precursor
IL-3
Pre B Cell
Prothymocyte
IL-7
IL-7
IL-15
B Lymphoblast
T Lymphoblast
Antigen
Driven
Antigen
Driven
Myeloblast
Flt3L
IL-1
IL-3
IL-6
IL-7
IL-10
SCF
G-CSF
IL-15
IL-3
Basophilic
Myelocyte
SCF
IL-3
Mature NK Cell (I)
Flt3L
IL-7
IL-15
IL-2
IFN
IL-3
T Cell
B. Metamyelocyte
IL-3
Mature NK Cell (II)
GM-CSF
IL-4
IL-1
IL-6
IL-12
TNF
Platelets
DC Stem Cell
Lymphoid-related
Dendritic Cell
GM-CSF
G-CSF
Erythrocyte
T Stem Cell
Myeloblast
Monoblast
N. Metamyelocyte
Megakaryocyte
G-CSF
IL-7
Progenitor
B Cell
Proerythroblast
IL-1
IL-6
IL-3
SCF
B Stem Cell
GM-CSF
G-CSF
GM-CSF
IL-3
SCF
EPO
SCF
Flt3L
IL-6
IL-7
IL-3
GM-CSF
IL-3
SCF
Flt3L
BFU-E
GM-CSF
IL-3
IL-1
IL-2
Plasma Cell
Band Basophil
IL-3
Basophil
Mast Cell
Legend
Pluripotent Stem Cell: The most primitive blood-forming cell,
primarily found in the bone marrow with small proportions found
in the blood and spleen. This cell has extensive self-renewal
capabilities and differentiates into lymphoid stem cells and
myeloid stem cells (CFU-GEMM).
Myeloid Stem Cell/CFU-GEMM (Colony-Forming Unit- Granulocyte,
Erythroid, Macrophage, Megakaryocyte):
Primitive blood-forming cell with extensive proliferative capacity
that differentiates into the committed precursors of granulocytes
(basophils, eosinophils, mast cells, and neutrophils), red blood
cells, monocyte/macrophages, dendritic cells, and platelets.
BFU-E/Burst-Forming Unit – Erythroid: The most primitive
committed progenitor of red blood cells. This cell has extensive
proliferative capacity and differentiates into CFU-E.
BFU-MK/Burst-Forming Unit – Megakaryocyte: The most
primitive committed precursor of platelets. This cell has high
proliferative capacity and differentiates into CFU-MK.
CFU-Bas/Colony-Forming Unit – Basophil: Committed
precursor of basophils with limited proliferative capacity.
CFU-E/Colony-Forming Unit – Erythroid: Committed precursor
of red blood cells with limited proliferative capacity.
CFU-Eo/Colony-Forming Unit – Eosinophil: Committed
precursor of eosinophils with limited proliferative capacity.
CFU-G/Colony-Forming Unit – Granulocyte: Committed
precursor of granulocytes with limited proliferative capacity.
CFU-GM/Colony-Forming Unit – Granulocyte-Macrophage:
Committed precursor of granulocytes, monocytes/macrophages,
and dendritic cells with limited proliferative capacity.
CFU-M/DC/Colony-Forming Unit – Monocyte/Dendritic Cell:
Committed precursor of monocytes/macrophages and dendritic
cells with limited proliferative capacity.
CFU-Mast/Colony-Forming Unit – Mast Cell: Committed
precursor of mast cells with limited proliferative capacity.
CFU-MK/Colony-Forming Unit – Megakaryocyte: Committed
precursor of platelets with limited proliferative capacity.
Band Neutrophil: Neutrophil precursor that develops from neutrophilic
metamyelocyte. Characterized by horse shoe shaped nuclei.
Basophil: White blood cell involved in inflammatory and anti-parasitic
responses. Basophils make up about 0.5% of the white blood cell count.
Basophilic Myelocyte: Immature cell that develops into a basophil.
Dendritic Cell: Professional antigen-presenting cell responsible for
induction of primary antigen-specific immune response.
E Metamyelocyte: Eosinophil precursor that develops from
eosinophilic myelocyte. Characterized by bean shaped nuclei and
eosinophilic granules.
Eosinophil: White blood cell important in anti-parasitic defense.
Makes up 1%-3% of the white blood cell count.
Platelet: Circulating cell important in the clotting process.
IL-18: Upregulates IFN production; enhances NK-cell cytotoxicity
Proerythroblast: Immature cell that develops into a red blood cell,
or erythrocyte.
IFN (Interferon): Stimulates macrophage and NK-cell activity;
stimulates T-cell growth and differentiation; provides direct
antitumor effects
Promonocyte: Immature cell that develops into a monocyte.
T Cell: Mature lymphoid cell responsible for control of the immune
response. Includes T-suppressor, T-helper, and T-cytotoxic “killer”
cells. Found in spleen, blood, and lymphatic system.
T Lymphoblast: Immature cell that develops into a T cell.
FACTORS
EPO: Erythropoietin
TPO: Thrombopoietin
Erythrocyte: Red blood cell responsible for oxygen transport.
G-CSF: Granulocyte Colony-Stimulating Factor
Lymphoid Stem Cell: Stem cell that upon differentiation gives rise to
lymphocytes. Includes B, T, and DC stem cells.
M-CSF: Macrophage Colony-Stimulating Factor
Mast Cell: White blood cell that proliferates during inflammatory
response. Found in connective tissues and plays a role in
allergic reactions.
IL-1: Upregulates adhesion molecule expression and neutrophil and
macrophage emigration; raises body temperature; facilitates hematopoiesis
IL-2: Stimulates T-cell activation and proliferation, B-cell growth,
and NK-cell proliferation and activation
IL-3: Promotes proliferation of hematopoietic progenitor cells
Megakaryocyte: Large multi-nucleated cell from which platelets
are derived.
IL-4: Stimulates differentiation and proliferation of TH2 helper
T-cells; stimulates B-cell Ig class switch to IgG1 and IgE
Monoblast: Immature cell that ultimately gives rise to a monocyte.
IL-5: Stimulates B-cell growth and eosinophil differentiation
and proliferation
Monocyte: Phagocytic cell that circulates in the bloodstream for
1-2 days. Upon migration to tissues, differentiates into the more
phagocytic macrophage.
Myeloblast: Immature cell that ultimately gives rise to a neutrophil.
N Metamyelocyte: Neutrophil precursor that develops from
neutrophilic myelocyte. Characterized by bean shaped nuclei and
neutrophilic granules.
Akashi K, Traver D, Miyamoto T, Weissman I. A clonogenic common myeloid progenitor that gives
rise to all myeloid lineages. Nature. 2000;404:193-197.
Arinobu Y, Iwasaki H, Akashi K. Origin of basophils and mast cells. Allergol Int. 2009;58(1):21-8.
Arinobu, Y, Iwasaki H, Gurish MF, Mizuno S, Shigematsu H, Ozawa H, Tenen DG, Austen KF, Akashi
K. Developmental checkpoints of the basophil/mast cell lineages in adult murine hematopoiesis.
Proc Natl Acad Sci USA. 2005;102(50):18105–18110.
Blom B, Spits H. Development of Human Lymphoid Cells. Annu. Rev. Immunol. 2006; 24:287–320.
Bondurant M, Koury M. Origin and development of blood cells. In: Greer J, Foerster J, Rodgers
G, Paraskevas F, Glader B, Foerster J, Lukens J, eds. Wintrobe’s Clinical Hematology. 11th ed.
Philadelphia, PA: Lippincott Williams & Wilkins; 2004:170.
Hirayama F, Ogawa M. Cytokine regulation of early lymphohematopoietic development.
Stem Cells.1996;14(4):369-75.
Hoffman R, Murray L, Young J, Luens K, Bruno E. Hierarchical Structure of Human Megakaryocyte
Progenitor Cells. Stem Cells. 1996;14(suppl 1):75-81.
Jacobsen SE, Borge OJ, Ramsfjell V, Cui L, Cardier JE, Veiby OP, Murphy MJ Jr, Lok S.
Thrombopoietin, a direct stimulator of viability and multilineage growth of primitive bone marrow
progenitor cells. Stem Cells. 1996;14 Suppl 1:173-80.
Kaushansky K. Lineage-specific hematopoietic growth factors. N Engl J Med. 2006;354(19):
2034-2045.
IL-7: Promotes differentiation of B-, T-, and NK-cell precursors and
activation of T and NK cells
Kent D, Copley M, Benz C, Dykstra B, Bowie M, Eaves C. Regulation of hematopoietic stem cells by
the steel factor/KIT signaling pathway. Clin Cancer Res. 2008;14(7):1926-30.
IL-10: Inhibits macrophage proinflammatory cytokine production;
downregulates cytokine class II antigen and B7-1 and B7-2
expression; inhibits differentiation of TH1 T-helper cells; inhibits
NK-cell function; stimulates mast cell proliferation and function
and B-cell activation and differentiation
Kikushige Y, Yoshimoto G, Miyamoto T, et al. Human flt3 is expressed at the hematopoietic stem cell
and the granulocyte/macrophage progenitor stages to maintain cell survival. J Immunol.
IL-11: Key regulator of multiple events in hematopoiesis, most
notably the stimulation of megakaryocyte maturation
Mori Y, Iwasaki H, Kohno K, Yoshimoto G, Kikushige Y, Okeda A, Uike N, Niiro H, Takenaka K,
Nagafuji K, Miyamoto T, Harada M, Takatsu K, Akashi K. Identification of the human eosinophil
lineage-committed progenitor: revision of phenotypic definition of the human common myeloid
progenitor. J Exp Med. 2009;206(1):183-93.
B Metamyelocyte: Basophil precursor that develops from
basophilic myelocyte. Characterized by bean shaped nuclei and
basophilic granules.
Neutrophil: White blood cell capable of phagocytosis, chemotaxis, and
adherence to immune complexes. Accounts for 60%-70% of the white
blood cell count.
IL-12: Secreted by activated macrophages, IL-12 induces TH1 T-helper
cell formation and lymphokine-activated killer cell formation; increases
CD8+CTL activity
Band Basophil: Immediate precursor of mature basophil that develops
from basophilic metamyelocyte. Characterized by horse shoe shaped nuclei.
Neutrophilic Myelocyte: Immature cell that develops into a neutrophil.
IL-15: Stimulates T-cell activation and proliferation; promotes
cytogenesis and NK cells
Band Eosinophil: Immediate precursor of mature eosinophils that develops
from eosinophilic metamyelocyte. Characterized by horse shoe
shaped nuclei.
REFERENCES
Kaushansky K. Hemopoeitic stem cells, progenitors and cytokines. In: Beutler E, Lichtman M,
Kaushansky K, Prchal J, Kipps T, Seligsohn U, eds. Williams Hematology. 7th ed. New York, NY:
McGraw-Hill; 2006:202.
B Lymphoblast: Immature cell that develops into a B cell.
Plasma Cell: B cell that manufactures immunoglobulins.
Flt3L: Ligand for Flt3 receptor
IL-6: Provokes a broad range of cellular and physiological responses
and plays a role in inflammation and hematopoiesis
Natural Killer (NK) Cells: Large granular lymphocyte which does not
express markers of either T or B cell lineage. These cells primarily kill
target cells using antibody-dependent cell-mediated cytotoxicity; however, other processes can be used to kill cells in the absence of
an antibody. Killing may occur without previous sensitization.
B Cell: Mature lymphoid cell involved in humoral immunity,
capable of differentiating into plasma cells that produce antibodies.
B cells are found in the spleen, blood, and lymphatic system.
SCF: Stem cell factor, ligand for c-kit receptor
GM-CSF: Granulocyte-Macrophage Colony-Stimulating Factor
Eosinophilic Myelocyte: Immature cell that develops into an eosinophil.
Macrophage: Phagocytic cell found in the tissues that is able to kill
bacteria, parasites, and fungi. Functions as an antigen-presenting cell
and regulates the inflammatory response.
TNF (Tumor Necrosis Factor): Promotes fever, anorexia, shock,
capillary leak syndrome, enhanced leukocyte cytotoxicity, and
enhanced NK-cell function
Majka, M, Janowska-Wieczorek A, Ratajczak J, Ehrenman K, Pietrzkowski Z, Kowalska A, Gewirtz G,
Emerson SG, Ratajczak MZ. Numerous growth factors, cytokines, and chemokines are secreted by
human CD341 cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal
hematopoiesis in an autocrine/paracrine manner. Blood. 2001; 97(10):3075-3085.
2008;180(11):7358–7367.
Ogawa M. Differentiation and proliferation of hematopoietic stem cells. Blood.
1993;81(11):2844-2853.
Williams D, Bunn HF, Sieff C, Zon L. Hematopoiesis. In: Handin R, Lux S, Stossel T, eds. Blood:
principles and practice of hematology. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins;
2003:181.