Cell-autonomous megakaryopoiesis associated with polyclonal hematopoiesis in triple-negative essential thrombocythemia
In: Scientific Reports Scientific Reports, Jg. 11 (2021), Heft 1, S. 1-11
Online
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Zugriff:
A subset of essential thrombocythemia (ET) cases are negative for disease-defining mutations on JAK2, MPL, and CALR and defined as triple negative (TN). The lack of recurrent mutations in TN-ET patients makes its pathogenesis ambiguous. Here, we screened 483 patients with suspected ET in a single institution, centrally reviewed bone marrow specimens, and identified 23 TN-ET patients. Analysis of clinical records revealed that TN-ET patients were mostly young female, without a history of thrombosis or progression to secondary myelofibrosis and leukemia. Sequencing analysis and human androgen receptor assays revealed that the majority of TN-ET patients exhibited polyclonal hematopoiesis, suggesting a possibility of reactive thrombocytosis in TN-ET. However, the serum levels of thrombopoietin (TPO) and interleukin-6 in TN-ET patients were not significantly different from those in ET patients with canonical mutations and healthy individuals. Rather, CD34-positive cells from TN-ET patients showed a capacity to form megakaryocytic colonies, even in the absence of TPO. No signs of thrombocytosis were observed before TN-ET development, denying the possibility of hereditary thrombocytosis in TN-ET. Overall, these findings indicate that TN-ET is a distinctive disease entity associated with polyclonal hematopoiesis and is paradoxically caused by hematopoietic stem cells harboring a capacity for cell-autonomous megakaryopoiesis.
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Cell-autonomous megakaryopoiesis associated with polyclonal hematopoiesis in triple-negative essential thrombocythemia
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Autor/in / Beteiligte Person: | Imai, Misa ; Ito, Masafumi ; Misawa, Kyohei ; Okuda, Maho ; Edahiro, Yoko ; Ochiai, Tomonori ; Kihara, Yoshihiko ; Komatsu, Norio ; Ando, Jun ; Yang, Yinjie ; Morishita, Soji ; Osaga, Satoshi ; Fukuda, Yasutaka ; Inano, Tadaaki ; Araki, Marito ; Mano, Hiroyuki |
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Zeitschrift: | Scientific Reports Scientific Reports, Jg. 11 (2021), Heft 1, S. 1-11 |
Veröffentlichung: | Springer Science and Business Media LLC, 2021 |
Medientyp: | unknown |
ISSN: | 2045-2322 (print) |
DOI: | 10.1038/s41598-021-97106-9 |
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