{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:34:03Z","timestamp":1788240843537,"version":"build-2803163510"},"reference-count":57,"publisher":"Georg Thieme Verlag KG","issue":"02","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81820108004"],"award-info":[{"award-number":["81820108004"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81800146"],"award-info":[{"award-number":["81800146"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"crossref","award":["LY20H080008"],"award-info":[{"award-number":["LY20H080008"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"crossref","award":["LY19H080009"],"award-info":[{"award-number":["LY19H080009"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"crossref","award":["LY16H160009"],"award-info":[{"award-number":["LY16H160009"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ibrutinib, an irreversible inhibitor of Bruton's tyrosine kinase, has a favorable safety profile in patients with B cell-related malignancies. A primary adverse effect of ibrutinib is thrombocytopenia in the early stages of treatment, but platelet counts increase or recover as treatment continues. Currently, the effects of ibrutinib on megakaryopoiesis remain unclear. In this study, we investigated the mechanism by which ibrutinib induces thrombocytopenia using cord blood CD34+ hematopoietic stem cells (HSCs), a human megakaryoblastic cell line (SET-2), and C57BL\/6 mice. We show that treatment with ibrutinib can suppress CD34+ HSC differentiation into megakaryocytes (MKs) and decrease the number of colony-forming unit-MKs (CFU-MKs). The ibrutinib-dependent inhibition of early megakaryopoiesis seems to mainly involve impaired proliferation of progenitor cells without induction of apoptosis. The effects of ibrutinib on late-stage megakaryopoiesis, in contrast to early-stage megakaryopoiesis, include enhanced MK differentiation, ploidy, and proplatelet formation in CD34+ HSC-derived MKs and SET-2 cells. We also demonstrated that MK adhesion and spreading, but not migration, were inhibited by ibrutinib. Furthermore, we revealed that integrin \u03b1IIb\u03b23 outside-in signaling in MKs was inhibited by ibrutinib. Consistent with previous clinical observations, in C57BL\/6 mice treated with ibrutinib, platelet counts decreased by days 2 to 7 and recovered to normal levels by day 15. Together, these results reveal the pathogenesis of ibrutinib-induced transient thrombocytopenia. In conclusion, ibrutinib suppresses early megakaryopoiesis, as evidenced by inhibition of MK progenitor cell proliferation and CFU-MK formation. Ibrutinib enhances MK differentiation, ploidy, and proplatelet formation, while it impairs integrin \u03b1IIb\u03b23 outside-in signaling.<\/jats:p>","DOI":"10.1055\/s-0040-1716530","type":"journal-article","created":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T23:14:58Z","timestamp":1600816498000},"page":"192-205","source":"Crossref","is-referenced-by-count":8,"title":["Ibrutinib Suppresses Early Megakaryopoiesis but Enhances Proplatelet Formation"],"prefix":"10.1055","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0821-2801","authenticated-orcid":false,"given":"Jiansong","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"},{"name":"Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang Province, China"},{"name":"Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujuan","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"},{"name":"Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang Province, China"},{"name":"Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixin","family":"Ma","sequence":"additional","affiliation":[{"name":"Clinical Prenatal Diagnosis Center, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangjie","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"},{"name":"Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang Province, China"},{"name":"Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"},{"name":"Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang Province, China"},{"name":"Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"},{"name":"Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang Province, China"},{"name":"Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"},{"name":"Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang Province, China"},{"name":"Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenle","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"},{"name":"Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang Province, China"},{"name":"Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daqiang","family":"He","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"},{"name":"Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang Province, China"},{"name":"Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"},{"name":"Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang Province, China"},{"name":"Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Ling","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"},{"name":"Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang Province, China"},{"name":"Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenglin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"},{"name":"Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang Province, China"},{"name":"Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihui","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"},{"name":"Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang Province, China"},{"name":"Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huafeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"},{"name":"Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang Province, China"},{"name":"Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yungui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"},{"name":"Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang Province, China"},{"name":"Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8166-9915","authenticated-orcid":false,"given":"Jie","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"},{"name":"Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang Province, China"},{"name":"Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2020,9,22]]},"reference":[{"issue":"02","key":"ref1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1161\/CIRCRESAHA.117.310795","article-title":"Circulating platelets as mediators of immunity, inflammation, and thrombosis","volume":"122","author":"M Koupenova","year":"2018","journal-title":"Circ Res"},{"issue":"01","key":"ref2","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13045-019-0709-6","article-title":"Platelet integrin \u03b1IIb\u03b23: signal transduction, regulation, and its therapeutic targeting","volume":"12","author":"J Huang","year":"2019","journal-title":"J Hematol Oncol"},{"issue":"03","key":"ref3","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1182\/blood-2007-05-088500","article-title":"Historical review: megakaryopoiesis and thrombopoiesis","volume":"111","author":"K Kaushansky","year":"2008","journal-title":"Blood"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"e32","DOI":"10.1017\/S1462399411002043","article-title":"Normal and malignant megakaryopoiesis","volume":"13","author":"Q Wen","year":"2011","journal-title":"Expert Rev Mol Med"},{"issue":"01","key":"ref5","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1038\/s41467-017-01690-2","article-title":"Critical role of the HDAC6-cortactin axis in human megakaryocyte maturation leading to a proplatelet-formation defect","volume":"8","author":"K Messaoudi","year":"2017","journal-title":"Nat Commun"},{"issue":"06","key":"ref6","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1083\/jcb.201304054","article-title":"The incredible journey: from megakaryocyte development to platelet formation","volume":"201","author":"K R Machlus","year":"2013","journal-title":"J Cell Biol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nature21706","article-title":"The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors","volume":"544","author":"E Lefran\u00e7ais","year":"2017","journal-title":"Nature"},{"issue":"09","key":"ref8","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1182\/blood-2016-11-752840","article-title":"Selinexor-induced thrombocytopenia results from inhibition of thrombopoietin signaling in early megakaryopoiesis","volume":"130","author":"K R Machlus","year":"2017","journal-title":"Blood"},{"issue":"07","key":"ref9","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.exphem.2012.02.004","article-title":"Panobinostat (LBH589)-induced acetylation of tubulin impairs megakaryocyte maturation and platelet formation","volume":"40","author":"C Iancu-Rubin","year":"2012","journal-title":"Exp Hematol"},{"issue":"10","key":"ref10","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.3324\/haematol.2018.188227","article-title":"Immunomodulatory drugs downregulate IKZF1 leading to expansion of hematopoietic progenitors with concomitant block of megakaryocytic maturation","volume":"103","author":"A Liu","year":"2018","journal-title":"Haematologica"},{"issue":"02","key":"ref11","first-page":"337","article-title":"The effect of decitabine on megakaryocyte maturation and platelet release","volume":"106","author":"J Wang","year":"2011","journal-title":"Thromb Haemost"},{"issue":"12","key":"ref12","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.3324\/haematol.2016.146746","article-title":"Revealing eltrombopag's promotion of human megakaryopoiesis through AKT\/ERK-dependent pathway activation","volume":"101","author":"C A Di Buduo","year":"2016","journal-title":"Haematologica"},{"issue":"11","key":"ref13","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1161\/ATVBAHA.115.306130","article-title":"Ibrutinib inhibits platelet integrin \u03b1IIb\u03b23 outside-in signaling and thrombus stability but not adhesion to collagen","volume":"35","author":"A P Bye","year":"2015","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"01","key":"ref14","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1056\/NEJMoa1215637","article-title":"Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia","volume":"369","author":"J C Byrd","year":"2013","journal-title":"N Engl J Med"},{"issue":"03","key":"ref15","doi-asserted-by":"crossref","first-page":"e124","DOI":"10.3324\/haematol.2015.140558","article-title":"Response to comment on incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib","volume":"101","author":"A H Lipsky","year":"2016","journal-title":"Haematologica"},{"issue":"26","key":"ref16","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1056\/NEJMoa1812836","article-title":"Ibrutinib regimens versus chemoimmunotherapy in older patients with untreated CLL","volume":"379","author":"J A Woyach","year":"2018","journal-title":"N Engl J Med"},{"issue":"24","key":"ref17","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1182\/blood-2017-09-808808","article-title":"Oral Bruton tyrosine kinase inhibitors selectively block atherosclerotic plaque-triggered thrombus formation in humans","volume":"131","author":"K Busygina","year":"2018","journal-title":"Blood"},{"issue":"03","key":"ref18","doi-asserted-by":"crossref","first-page":"e119","DOI":"10.3324\/haematol.2017.179044","article-title":"Ibrutinib does not affect ristocetin-induced platelet aggregation evaluated by light transmission aggregometry in chronic lymphocytic leukemia patients","volume":"103","author":"M A Alberelli","year":"2018","journal-title":"Haematologica"},{"issue":"26","key":"ref19","doi-asserted-by":"crossref","first-page":"2610","DOI":"10.1182\/bloodadvances.2017011999","article-title":"Severe platelet dysfunction in NHL patients receiving ibrutinib is absent in patients receiving acalabrutinib","volume":"1","author":"A P Bye","year":"2017","journal-title":"Blood Adv"},{"issue":"03","key":"ref20","doi-asserted-by":"crossref","first-page":"e89","DOI":"10.3324\/haematol.2016.155978","article-title":"Effects of ibrutinib treatment on murine platelet function during inflammation and in primary hemostasis","volume":"102","author":"R H Lee","year":"2017","journal-title":"Haematologica"},{"issue":"26","key":"ref21","doi-asserted-by":"crossref","first-page":"3991","DOI":"10.1182\/blood-2014-06-583294","article-title":"Ibrutinib treatment affects collagen and von Willebrand factor-dependent platelet functions","volume":"124","author":"M Levade","year":"2014","journal-title":"Blood"},{"issue":"02","key":"ref22","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1080\/10428194.2017.1339874","article-title":"Atrial fibrillation as a complication of ibrutinib therapy: clinical features and challenges of management","volume":"59","author":"B C Thorp","year":"2018","journal-title":"Leuk Lymphoma"},{"issue":"06","key":"ref23","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1182\/blood-2015-03-635326","article-title":"Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results","volume":"126","author":"M L Wang","year":"2015","journal-title":"Blood"},{"issue":"25","key":"ref24","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1056\/NEJMoa1509388","article-title":"Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia","volume":"373","author":"J A Burger","year":"2015","journal-title":"N Engl J Med"},{"issue":"15","key":"ref25","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1056\/NEJMoa1501548","article-title":"Ibrutinib in previously treated Waldenstr\u00f6m's macroglobulinemia","volume":"372","author":"S P Treon","year":"2015","journal-title":"N Engl J Med"},{"issue":"12","key":"ref26","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1111\/cas.13076","article-title":"Efficacy and safety of ibrutinib in Japanese patients with relapsed or refractory mantle cell lymphoma","volume":"107","author":"D Maruyama","year":"2016","journal-title":"Cancer Sci"},{"issue":"12","key":"ref27","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.3324\/haematol.2015.126672","article-title":"Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib","volume":"100","author":"A H Lipsky","year":"2015","journal-title":"Haematologica"},{"issue":"16","key":"ref28","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1182\/blood-2014-10-606038","article-title":"Three-year follow-up of treatment-na\u00efve and previously treated patients with CLL and SLL receiving single-agent ibrutinib","volume":"125","author":"J C Byrd","year":"2015","journal-title":"Blood"},{"issue":"05","key":"ref29","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1182\/blood-2005-11-011957","article-title":"Regulation of proplatelet formation and platelet release by integrin \u03b1 IIb \u03b23","volume":"108","author":"M K Larson","year":"2006","journal-title":"Blood"},{"issue":"02","key":"ref30","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/ajh.24958","article-title":"Mutations of the integrin \u03b1IIb\/\u03b23 intracytoplasmic salt bridge cause macrothrombocytopenia and enlarged platelet \u03b1-granules","volume":"93","author":"M Favier","year":"2018","journal-title":"Am J Hematol"},{"issue":"03","key":"ref31","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1097\/MBC.0000000000000241","article-title":"Abnormal cytoplasmic extensions associated with active \u03b1IIb\u03b23 are probably the cause for macrothrombocytopenia in Glanzmann thrombasthenia-like syndrome","volume":"26","author":"H Hauschner","year":"2015","journal-title":"Blood Coagul Fibrinolysis"},{"issue":"04","key":"ref32","doi-asserted-by":"crossref","first-page":"e34449","DOI":"10.1371\/journal.pone.0034449","article-title":"Outside-in signalling generated by a constitutively activated integrin \u03b1IIb\u03b23 impairs proplatelet formation in human megakaryocytes","volume":"7","author":"L Bury","year":"2012","journal-title":"PLoS One"},{"issue":"05","key":"ref33","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1111\/jth.14424","article-title":"First description of an IgM monoclonal antibody causing \u03b1IIb \u03b23 integrin activation and acquired Glanzmann thrombasthenia associated with macrothrombocytopenia","volume":"17","author":"X Pillois","year":"2019","journal-title":"J Thromb Haemost"},{"issue":"20","key":"ref34","doi-asserted-by":"crossref","first-page":"5479","DOI":"10.1182\/blood-2010-12-323691","article-title":"Heterozygous ITGA2B R995W mutation inducing constitutive activation of the \u03b1IIb\u03b23 receptor affects proplatelet formation and causes congenital macrothrombocytopenia","volume":"117","author":"S Kunishima","year":"2011","journal-title":"Blood"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"297","DOI":"10.3389\/fphar.2018.00297","article-title":"D-dencichine regulates thrombopoiesis by promoting megakaryocyte adhesion, migration and proplatelet formation","volume":"9","author":"S Ding","year":"2018","journal-title":"Front Pharmacol"},{"issue":"130","key":"ref36","first-page":"e56420","article-title":"Megakaryocyte differentiation and platelet formation from human cord blood-derived CD34+ cells","volume":"130","author":"J Perdomo","year":"2017","journal-title":"J Vis Exp"},{"issue":"04","key":"ref37","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1080\/09537104.2018.1430359","article-title":"A novel method for automated assessment of megakaryocyte differentiation and proplatelet formation","volume":"29","author":"M Salzmann","year":"2018","journal-title":"Platelets"},{"issue":"19","key":"ref38","doi-asserted-by":"crossref","first-page":"5198","DOI":"10.1182\/blood-2010-12-326850","article-title":"Dasatinib enhances megakaryocyte differentiation but inhibits platelet formation","volume":"117","author":"A Mazharian","year":"2011","journal-title":"Blood"},{"issue":"05","key":"ref39","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1182\/blood-2010-03-275990","article-title":"Critical role of Src-Syk-PLC\u03b32 signaling in megakaryocyte migration and thrombopoiesis","volume":"116","author":"A Mazharian","year":"2010","journal-title":"Blood"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.ebiom.2018.01.031","article-title":"High expression of TET1 predicts poor survival in cytogenetically normal acute myeloid leukemia from two cohorts","volume":"28","author":"J Wang","year":"2018","journal-title":"EBioMedicine"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s13045-015-0159-8","article-title":"Evaluation of targeting c-Src by the RGT-containing peptide as a novel antithrombotic strategy","volume":"8","author":"J Huang","year":"2015","journal-title":"J Hematol Oncol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13045-016-0244-7","article-title":"H2S protects against fatal myelosuppression by promoting the generation of megakaryocytes\/platelets","volume":"9","author":"H D Liu","year":"2016","journal-title":"J Hematol Oncol"},{"issue":"02","key":"ref43","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1182\/blood-2014-12-614677","article-title":"VPS33B regulates protein sorting into and maturation of \u03b1-granule progenitor organelles in mouse megakaryocytes","volume":"126","author":"D Bem","year":"2015","journal-title":"Blood"},{"issue":"06","key":"ref44","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1111\/bjh.12709","article-title":"Rho kinase inhibition drives megakaryocyte polyploidization and proplatelet formation through MYC and NFE2 downregulation","volume":"164","author":"M P Avanzi","year":"2014","journal-title":"Br J Haematol"},{"issue":"11","key":"ref45","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1111\/j.1538-7836.2008.03132.x","article-title":"Adhesive receptors, extracellular proteins and myosin IIA orchestrate proplatelet formation by human megakaryocytes","volume":"6","author":"A Balduini","year":"2008","journal-title":"J Thromb Haemost"},{"issue":"14","key":"ref46","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1182\/blood-2017-03-773614","article-title":"Integrin \u03b1IIb\u03b23 outside-in signaling","volume":"130","author":"T N Durrant","year":"2017","journal-title":"Blood"},{"issue":"04","key":"ref47","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1101\/gad.1758709","article-title":"Genetic and cell biological analysis of integrin outside-in signaling","volume":"23","author":"K R Legate","year":"2009","journal-title":"Genes Dev"},{"issue":"01","key":"ref48","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/S1470-2045(13)70513-8","article-title":"Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b\/2 trial","volume":"15","author":"S O'Brien","year":"2014","journal-title":"Lancet Oncol"},{"issue":"03","key":"ref49","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/leu.2015.175","article-title":"Ibrutinib selectively targets FLT3-ITD in mutant FLT3-positive AML","volume":"30","author":"H Wu","year":"2016","journal-title":"Leukemia"},{"issue":"07","key":"ref50","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1007\/s40266-017-0468-4","article-title":"Current status of Bruton's tyrosine kinase inhibitor development and use in B-cell malignancies","volume":"34","author":"A Aw","year":"2017","journal-title":"Drugs Aging"},{"issue":"04","key":"ref51","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1007\/s00432-017-2570-8","article-title":"Promising efficacy of novel BTK inhibitor AC0010 in mantle cell lymphoma","volume":"144","author":"X Yan","year":"2018","journal-title":"J Cancer Res Clin Oncol"},{"issue":"02","key":"ref52","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1111\/jth.12469","article-title":"MiR-9 contributes to the developmental differences in CXCR-4 expression in human megakaryocytes","volume":"12","author":"F Ferrer-Marin","year":"2014","journal-title":"J Thromb Haemost"},{"issue":"13","key":"ref53","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1182\/blood-2014-01-453134","article-title":"Src family kinases: at the forefront of platelet activation","volume":"124","author":"Y A Senis","year":"2014","journal-title":"Blood"},{"issue":"06","key":"ref54","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1182\/bloodadvances.2017010975","article-title":"Enhancing functional platelet release in vivo from in vitro-grown megakaryocytes using small molecule inhibitors","volume":"2","author":"D Jarocha","year":"2018","journal-title":"Blood Adv"},{"issue":"12","key":"ref55","doi-asserted-by":"crossref","first-page":"2524","DOI":"10.1111\/jth.13519","article-title":"The cell division control protein 42-Src family kinase-neural Wiskott-Aldrich syndrome protein pathway regulates human proplatelet formation","volume":"14","author":"A Palazzo","year":"2016","journal-title":"J Thromb Haemost"},{"issue":"06","key":"ref56","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1111\/bjh.12974","article-title":"Characterization of ibrutinib-sensitive and -resistant mantle lymphoma cells","volume":"166","author":"J Ma","year":"2014","journal-title":"Br J Haematol"},{"key":"ref57","first-page":"267","volume-title":"Fetal and neonatal megakaryopoiesis and platelet biology","author":"C Dame","year":"2016"}],"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0040-1716530.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T03:03:45Z","timestamp":1612235025000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0040-1716530"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,22]]},"references-count":57,"journal-issue":{"issue":"02","published-online":{"date-parts":[[2021,2,1]]},"published-print":{"date-parts":[[2021,2]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0040-1716530","relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,22]]}}}