Megakaryocytopoiesis involves the commitment of haematopoietic stem cells, proliferation and terminal differentiation of megakaryocytic progenitors (MK-p) and maturation of megakaryocytes (MKs) to produce functional platelets. This complex process occurs in specialized niches in the bone marrow where MKs align adjacent to vascular endothelial cells, form proplatelet projections and release platelets into the circulation. Thrombopoietin (THPO, TPO) is the primary growth factor for the MK lineage and necessary at all stages of development. THPO is constitutively produced in the liver, and binds to MPL (c-Mpl) receptor on platelets and MKs. This activates a cascade of signalling molecules, which induce transcription factors to drive MK development and thrombopoiesis. Decreased turnover rate and platelet number result in increased levels of free THPO, which induces a concentration-dependant compensatory response of marrow-MKs to enhance platelet production. Newly developed thrombopoietic agents operating via MPL receptor facilitate platelet production in thrombocytopenic states, primarily immune thrombocytopenia. Other drugs are available for attenuating malignant thrombocytosis. Herein, we review the regulation of megakaryocytopoiesis and platelet production in normal and disease states, and the innovative drugs and therapeutic modalities to stimulate or decrease thrombopoiesis.
机构:
Beth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USABeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Afdhal, Nezam H.
;
Giannini, Edoardo G.
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Univ Genoa, Dept Internal Med, Gastroenterol Unit, I-16126 Genoa, ItalyBeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Giannini, Edoardo G.
;
Tayyab, Ghias
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Postgrad Med Inst, Dept Med Gastroenterol & Hepatol, Lahore, Pakistan
Lahore Gen Hosp, Lahore, PakistanBeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Tayyab, Ghias
;
Mohsin, Aftab
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Serv Inst Med Sci, Serv Hosp Lahore, Dept Gastroenterol, Lahore, PakistanBeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Mohsin, Aftab
;
Lee, Jin-Woo
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机构:
Inha Univ, Sch Med, Dept Internal Med, Div Hepatol, Inchon, South KoreaBeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Lee, Jin-Woo
;
Andriulli, Angelo
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Casa Sollievo Sofferenza Hosp, Div Gastroenterol, Dept Internal Med, San Giovanni Rotondo, ItalyBeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Andriulli, Angelo
;
Jeffers, Lennox
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机构:
Univ Miami, Miller Sch Med, Ctr Liver Dis, Miami, FL 33136 USABeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Jeffers, Lennox
;
McHutchison, John
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Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA
Duke Univ, Med Ctr, Div Gastroenterol, Durham, NC USABeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
McHutchison, John
;
Chen, Pei-Jer
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机构:
Natl Taiwan Univ, Coll Med, Hepatitis Res Ctr, Dept Internal Med,Grad Inst Clin Med, Taipei 10764, Taiwan
Natl Taiwan Univ Hosp, Taipei, TaiwanBeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Chen, Pei-Jer
;
Han, Kwang-Hyub
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Yonsei Univ, Coll Med, Yonsei Inst Gastroenterol, Yonsei Liver Canc Special Clin,Dept Internal Med, Seoul, South KoreaBeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Han, Kwang-Hyub
;
Campbell, Fiona
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GlaxoSmithKline Stockley Pk, Oncol Clin Dev, Uxbridge, Middx, EnglandBeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Campbell, Fiona
;
Hyde, Denise
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GlaxoSmithKline Stockley Pk, Oncol Clin Dev, Uxbridge, Middx, EnglandBeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Hyde, Denise
;
Brainsky, Andres
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GlaxoSmithKline Stockley Pk, Oncol Clin Dev, Collegeville, PA USABeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Brainsky, Andres
;
Theodore, Dickens
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GlaxoSmithKline Stockley Pk, Oncol Clin Dev, Res Triangle Pk, NC USABeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
机构:
Weill Cornell Med Coll, Div Hematol & Oncol, Dept Med, New York, NY 10065 USAWeill Cornell Med Coll, Div Hematol & Oncol, Dept Med, New York, NY 10065 USA
Basciano, Paul A.
;
Bussel, James B.
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Weill Cornell Med Coll, Div Hematol & Oncol, Dept Med, New York, NY 10065 USA
Weill Cornell Med Coll, Platelet Disorders Ctr, Dept Pediat, New York, NY 10065 USAWeill Cornell Med Coll, Div Hematol & Oncol, Dept Med, New York, NY 10065 USA
机构:
Beth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USABeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Afdhal, Nezam H.
;
Giannini, Edoardo G.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Genoa, Dept Internal Med, Gastroenterol Unit, I-16126 Genoa, ItalyBeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Giannini, Edoardo G.
;
Tayyab, Ghias
论文数: 0引用数: 0
h-index: 0
机构:
Postgrad Med Inst, Dept Med Gastroenterol & Hepatol, Lahore, Pakistan
Lahore Gen Hosp, Lahore, PakistanBeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Tayyab, Ghias
;
Mohsin, Aftab
论文数: 0引用数: 0
h-index: 0
机构:
Serv Inst Med Sci, Serv Hosp Lahore, Dept Gastroenterol, Lahore, PakistanBeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Mohsin, Aftab
;
Lee, Jin-Woo
论文数: 0引用数: 0
h-index: 0
机构:
Inha Univ, Sch Med, Dept Internal Med, Div Hepatol, Inchon, South KoreaBeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Lee, Jin-Woo
;
Andriulli, Angelo
论文数: 0引用数: 0
h-index: 0
机构:
Casa Sollievo Sofferenza Hosp, Div Gastroenterol, Dept Internal Med, San Giovanni Rotondo, ItalyBeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Andriulli, Angelo
;
Jeffers, Lennox
论文数: 0引用数: 0
h-index: 0
机构:
Univ Miami, Miller Sch Med, Ctr Liver Dis, Miami, FL 33136 USABeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Jeffers, Lennox
;
McHutchison, John
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机构:
Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA
Duke Univ, Med Ctr, Div Gastroenterol, Durham, NC USABeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
McHutchison, John
;
Chen, Pei-Jer
论文数: 0引用数: 0
h-index: 0
机构:
Natl Taiwan Univ, Coll Med, Hepatitis Res Ctr, Dept Internal Med,Grad Inst Clin Med, Taipei 10764, Taiwan
Natl Taiwan Univ Hosp, Taipei, TaiwanBeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Chen, Pei-Jer
;
Han, Kwang-Hyub
论文数: 0引用数: 0
h-index: 0
机构:
Yonsei Univ, Coll Med, Yonsei Inst Gastroenterol, Yonsei Liver Canc Special Clin,Dept Internal Med, Seoul, South KoreaBeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Han, Kwang-Hyub
;
Campbell, Fiona
论文数: 0引用数: 0
h-index: 0
机构:
GlaxoSmithKline Stockley Pk, Oncol Clin Dev, Uxbridge, Middx, EnglandBeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Campbell, Fiona
;
Hyde, Denise
论文数: 0引用数: 0
h-index: 0
机构:
GlaxoSmithKline Stockley Pk, Oncol Clin Dev, Uxbridge, Middx, EnglandBeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Hyde, Denise
;
Brainsky, Andres
论文数: 0引用数: 0
h-index: 0
机构:
GlaxoSmithKline Stockley Pk, Oncol Clin Dev, Collegeville, PA USABeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
Brainsky, Andres
;
Theodore, Dickens
论文数: 0引用数: 0
h-index: 0
机构:
GlaxoSmithKline Stockley Pk, Oncol Clin Dev, Res Triangle Pk, NC USABeth Israel Deaconess Med Ctr, Div Gastroenterol, Ctr Liver, Boston, MA 02215 USA
机构:
Weill Cornell Med Coll, Div Hematol & Oncol, Dept Med, New York, NY 10065 USAWeill Cornell Med Coll, Div Hematol & Oncol, Dept Med, New York, NY 10065 USA
Basciano, Paul A.
;
Bussel, James B.
论文数: 0引用数: 0
h-index: 0
机构:
Weill Cornell Med Coll, Div Hematol & Oncol, Dept Med, New York, NY 10065 USA
Weill Cornell Med Coll, Platelet Disorders Ctr, Dept Pediat, New York, NY 10065 USAWeill Cornell Med Coll, Div Hematol & Oncol, Dept Med, New York, NY 10065 USA