Anagrelide Modulates Proplatelet Formation Resulting in Decreased Number and Increased Size of Platelets

Miyashita, Naohiro; Onozawa, Masahiro; Yokoyama, Shota; Hidaka, Daisuke; Hayasaka, Koji; Kunishima, Shinji; Teshima, Takanori

doi:10.1097/hs9.0000000000000268

Cited by 4 publications

(3 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Abivertinib Inhibits Meg-01-derived Mk Differentiationmentioning

confidence: 99%

“…The differentiation of Meg-01 cells, a human megakaryoblastic cell line, can be induced by PMA, a TPO activator or protein kinase C signaling [35,36]. After PMA treatment, Meg-01 cells become larger, exhibit cytoplasmic extensions, and express the MK markers CD41a and CD61 [35]. Meg-01 cells were cultured with 10 nmol/L PMA in the presence or absence of abivertinib for four days to determine whether abivertinib could affect Meg-01-derived MK differentiation.…”

Section: Abivertinib Inhibits Meg-01-derived Mk Differentiationmentioning

confidence: 99%

See 1 more Smart Citation

Abivertinib inhibits megakaryocyte differentiation and platelet biogenesis

Huang

et al. 2021

Front. Med.

View full text Add to dashboard Cite

Abivertinib, a third-generation tyrosine kinase inhibitor, is originally designed to target epidermal growth factor receptor (EGFR)-activating mutations. Previous studies have shown that abivertinib has promising antitumor activity and a well-tolerated safety profile in patients with non-small-cell lung cancer. However, abivertinib also exhibited high inhibitory activity against Bruton's tyrosine kinase and Janus kinase 3. Given that these kinases play some roles in the progression of megakaryopoiesis, we speculate that abivertinib can affect megakaryocyte (MK) differentiation and platelet biogenesis. We treated cord blood CD34 + hematopoietic stem cells, Meg-01 cells, and C57BL/6 mice with abivertinib and observed megakaryopoiesis to determine the biological effect of abivertinib on MK differentiation and platelet biogenesis. Our in vitro results showed that abivertinib impaired the CFU-MK formation, proliferation of CD34 + HSC-derived MK progenitor cells, and differentiation and functions of MKs and inhibited Meg-01-derived MK differentiation. These results suggested that megakaryopoiesis was inhibited by abivertinib. We also demonstrated in vivo that abivertinib decreased the number of MKs in bone marrow and platelet counts in mice, which suggested that thrombopoiesis was also inhibited. Thus, these preclinical data collectively suggested that abivertinib could inhibit MK differentiation and platelet biogenesis and might be an agent for thrombocythemia.

show abstract

Section: Abivertinib Inhibits Meg-01-derived Mk Differentiationmentioning

confidence: 99%

Section: Abivertinib Inhibits Meg-01-derived Mk Differentiationmentioning

confidence: 99%

Abivertinib inhibits megakaryocyte differentiation and platelet biogenesis

Huang

et al. 2021

Front. Med.

View full text Add to dashboard Cite

show abstract

“…It has been estimated that a single MK can produce more than 3000 PPTs. The data accumulated to date indicate that 1 exerts an effect on MK proliferation and differentiation and modulates PPT formation, with a reduction in the number, size, and volume of MKs that equates to a 60% reduction in mass, which correlates with the observed fall in platelet count. − The effects of 1 on megakaryocyte function are phenotypically different from 3 , an inhibitor of ribonucleotide reductase that reduces the synthesis of deoxyribonucleotides. , …”

mentioning

confidence: 99%