Advances in megakaryocytopoiesis and thrombopoiesis: from bench to bedside

被引:75
作者
Deutsch, Varda R. [1 ]
Tomer, Aaron [1 ,2 ,3 ]
机构
[1] Tel Aviv Sourasky Med Ctr, Haematol Inst, IL-64239 Tel Aviv, Israel
[2] Ben Gurion Univ Negev, Fac Hlth Sci, Beer Sheva, Israel
[3] Soroka Univ, Med Ctr, Beer Sheva, Israel
关键词
megakaryocytes; megakaryocytopoiesis; thrombopoietin; mimetics; thrombopoiesis; CHRONIC IMMUNE THROMBOCYTOPENIA; RISK MYELODYSPLASTIC SYNDROME; CONGENITAL AMEGAKARYOCYTIC THROMBOCYTOPENIA; ACUTE MYELOID-LEUKEMIA; VENOUS THROMBOEMBOLISM; PLATELET PRODUCTION; DOUBLE-BLIND; LONG-TERM; HEREDITARY THROMBOCYTOSIS; POLYCYTHEMIA-VERA;
D O I
10.1111/bjh.12328
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:778 / 793
页数:16
相关论文
共 154 条
[1]   Eltrombopag before Procedures in Patients with Cirrhosis and Thrombocytopenia [J].
Afdhal, Nezam H. ;
Giannini, Edoardo G. ;
Tayyab, Ghias ;
Mohsin, Aftab ;
Lee, Jin-Woo ;
Andriulli, Angelo ;
Jeffers, Lennox ;
McHutchison, John ;
Chen, Pei-Jer ;
Han, Kwang-Hyub ;
Campbell, Fiona ;
Hyde, Denise ;
Brainsky, Andres ;
Theodore, Dickens .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 367 (08) :716-724
[2]   Deficiencies in progenitor cells of multiple hematopoietic lineages and defective megakaryocytopoiesis in mice lacking the thrombopoietin receptor c-mpl [J].
Alexander, WS ;
Roberts, AW ;
Nicola, NA ;
Li, RL ;
Metcalf, D .
BLOOD, 1996, 87 (06) :2162-2170
[3]   Reciprocal activation of GATA-1 and PU.1 marks initial specification of hematopoietic stem cells into myeloerythroid and myelolymphoid lineages [J].
Arinobu, Yojiro ;
Mizuno, Shin-ichi ;
Chong, Yong ;
Shigematsu, Hirokazu ;
Lino, Tadafumi ;
Iwasaki, Hiromi ;
Graf, Thomas ;
Mayfield, Robin ;
Chan, Susan ;
Kastner, Philippe ;
Akashi, Koichi .
CELL STEM CELL, 2007, 1 (04) :416-427
[4]   Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis [J].
Avecilla, ST ;
Hattori, K ;
Heissig, B ;
Tejada, R ;
Liao, F ;
Shido, K ;
Jin, DK ;
Dias, S ;
Zhang, F ;
Hartman, TE ;
Hackett, NR ;
Crystal, RG ;
Witte, L ;
Hicklin, DJ ;
Bohlen, P ;
Eaton, D ;
Lyden, D ;
de Sauvage, F ;
Rafii, S .
NATURE MEDICINE, 2004, 10 (01) :64-71
[5]   Congenital Amegakaryocytic Thrombocytopenia: Clinical Presentation, Diagnosis, and Treatment [J].
Ballmaier, Matthias ;
Germeshausen, Manuela .
SEMINARS IN THROMBOSIS AND HEMOSTASIS, 2011, 37 (06) :673-681
[6]   Front-line therapy in polycythemia vera and essential thrombocythemia [J].
Barbui, Tiziano ;
Finazzi, Maria Chiara ;
Finazzi, Guido .
BLOOD REVIEWS, 2012, 26 (05) :205-211
[7]  
Barosi G, 2012, EXPERT REV HEMATOL, V5, P313, DOI [10.1586/ehm.12.17, 10.1586/EHM.12.17]
[8]   Thrombopoietin-receptor agonists [J].
Basciano, Paul A. ;
Bussel, James B. .
CURRENT OPINION IN HEMATOLOGY, 2012, 19 (05) :392-398
[9]   The impact of thrombopoietin on clinical practice [J].
Basser, R .
CURRENT PHARMACEUTICAL DESIGN, 2002, 8 (05) :369-377
[10]   Romiplostim efficacy in an acute myeloid leukemia patient with transfusion refractory thrombocytopenia [J].
Berthelot-Richer, Maxime ;
Boilard, Brigitte ;
Morin, Annie ;
Bolduc, Brigitte ;
Beauregard, Patrice ;
Kotb, Rami .
TRANSFUSION, 2012, 52 (04) :739-741