Increase in Frequency of Myeloid-Derived Suppressor Cells in the Bone Marrow of Myeloproliferative Neoplasm: Potential Implications in Myelofibrosis
Само за регистроване кориснике
2023
Аутори
Kapor, SunčicaMomčilović, Sanja
Kapor, Slobodan
Mojsilović, Slavko
Radojković, Milica
Apostolović, Milica
Filipović, Branka
Gotić, Mirjana
Čokić, Vladan
Santibanez, Juan F.
Simon, Felipe
Поглавље у монографији (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
The Philadelphia-negative myeloproliferative neoplasms (MPNs), defined as clonal disorders of the hematopoietic stem cells, are characterized by the proliferation of mature myeloid cells in the bone marrow and a chronic inflammatory status impacting the initiation, progression, and symptomatology of the malignancies. There are three main entities defined as essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF), and genetically classified by JAK2V617F, CALR, or MPL mutations. In MPNs, due to the overproduction of inflammatory cytokines by the neoplastic cells and non-transformed immune cells, chronic inflammation may provoke the generation and expansion of myeloid-derived suppressors cells (MDSCs) that highly influence the adaptive immune response. Although peripheral blood MDSC levels are elevated, their frequency in the bone marrow of MPNs patients is not well elucidated yet. Our results indicated increased levels of total (T)-MDSCs (CD33+HLA-DR−/low)... and polymorphonuclear (PMN)-MDSCs (CD33+/HLA-DRlow/CD15+/CD14−) in the bone marrow and peripheral blood of all three types of MPNs malignancies. However, these bone marrow MDSCs-increased frequencies did not correlate with the clinical parameters, such as hepatomegaly, leukocytes, hemoglobin, or platelet levels, or with JAK2 and CALR mutations. Besides, bone marrow MDSCs, from ET, PV, and PMF patients, exhibited immunosuppressive function, determined as T-cell proliferation inhibition. Notably, the highest T-MDSCs and PMN-MDSC levels were found in PMF samples, and the increased MDSCs frequency strongly correlated with the degree of myelofibrosis. Thus, these data together indicate that the immunosuppressive MDSCs population is increased in the bone marrow of MPNs patients and may be implicated in generating a fibrotic microenvironment.
Кључне речи:
Bone-marrow / MDSCs / Immunosuppression / Fibrosis / And TGF-b1Извор:
Advances in Molecular Pathology, 2023, 1408, 273-290Издавач:
- Springer Nature
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200015 (Универзитет у Београду, Институт за медицинска истраживања) (RS-MESTD-inst-2020-200015)
Институција/група
Institut za medicinska istraživanjaTY - CHAP AU - Kapor, Sunčica AU - Momčilović, Sanja AU - Kapor, Slobodan AU - Mojsilović, Slavko AU - Radojković, Milica AU - Apostolović, Milica AU - Filipović, Branka AU - Gotić, Mirjana AU - Čokić, Vladan AU - Santibanez, Juan F. AU - Simon, Felipe PY - 2023 UR - http://rimi.imi.bg.ac.rs/handle/123456789/1391 AB - The Philadelphia-negative myeloproliferative neoplasms (MPNs), defined as clonal disorders of the hematopoietic stem cells, are characterized by the proliferation of mature myeloid cells in the bone marrow and a chronic inflammatory status impacting the initiation, progression, and symptomatology of the malignancies. There are three main entities defined as essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF), and genetically classified by JAK2V617F, CALR, or MPL mutations. In MPNs, due to the overproduction of inflammatory cytokines by the neoplastic cells and non-transformed immune cells, chronic inflammation may provoke the generation and expansion of myeloid-derived suppressors cells (MDSCs) that highly influence the adaptive immune response. Although peripheral blood MDSC levels are elevated, their frequency in the bone marrow of MPNs patients is not well elucidated yet. Our results indicated increased levels of total (T)-MDSCs (CD33+HLA-DR−/low) and polymorphonuclear (PMN)-MDSCs (CD33+/HLA-DRlow/CD15+/CD14−) in the bone marrow and peripheral blood of all three types of MPNs malignancies. However, these bone marrow MDSCs-increased frequencies did not correlate with the clinical parameters, such as hepatomegaly, leukocytes, hemoglobin, or platelet levels, or with JAK2 and CALR mutations. Besides, bone marrow MDSCs, from ET, PV, and PMF patients, exhibited immunosuppressive function, determined as T-cell proliferation inhibition. Notably, the highest T-MDSCs and PMN-MDSC levels were found in PMF samples, and the increased MDSCs frequency strongly correlated with the degree of myelofibrosis. Thus, these data together indicate that the immunosuppressive MDSCs population is increased in the bone marrow of MPNs patients and may be implicated in generating a fibrotic microenvironment. PB - Springer Nature T2 - Advances in Molecular Pathology T1 - Increase in Frequency of Myeloid-Derived Suppressor Cells in the Bone Marrow of Myeloproliferative Neoplasm: Potential Implications in Myelofibrosis EP - 290 SP - 273 VL - 1408 DO - 10.1007/978-3-031-26163-3_15 ER -
@inbook{ author = "Kapor, Sunčica and Momčilović, Sanja and Kapor, Slobodan and Mojsilović, Slavko and Radojković, Milica and Apostolović, Milica and Filipović, Branka and Gotić, Mirjana and Čokić, Vladan and Santibanez, Juan F. and Simon, Felipe", year = "2023", abstract = "The Philadelphia-negative myeloproliferative neoplasms (MPNs), defined as clonal disorders of the hematopoietic stem cells, are characterized by the proliferation of mature myeloid cells in the bone marrow and a chronic inflammatory status impacting the initiation, progression, and symptomatology of the malignancies. There are three main entities defined as essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF), and genetically classified by JAK2V617F, CALR, or MPL mutations. In MPNs, due to the overproduction of inflammatory cytokines by the neoplastic cells and non-transformed immune cells, chronic inflammation may provoke the generation and expansion of myeloid-derived suppressors cells (MDSCs) that highly influence the adaptive immune response. Although peripheral blood MDSC levels are elevated, their frequency in the bone marrow of MPNs patients is not well elucidated yet. Our results indicated increased levels of total (T)-MDSCs (CD33+HLA-DR−/low) and polymorphonuclear (PMN)-MDSCs (CD33+/HLA-DRlow/CD15+/CD14−) in the bone marrow and peripheral blood of all three types of MPNs malignancies. However, these bone marrow MDSCs-increased frequencies did not correlate with the clinical parameters, such as hepatomegaly, leukocytes, hemoglobin, or platelet levels, or with JAK2 and CALR mutations. Besides, bone marrow MDSCs, from ET, PV, and PMF patients, exhibited immunosuppressive function, determined as T-cell proliferation inhibition. Notably, the highest T-MDSCs and PMN-MDSC levels were found in PMF samples, and the increased MDSCs frequency strongly correlated with the degree of myelofibrosis. Thus, these data together indicate that the immunosuppressive MDSCs population is increased in the bone marrow of MPNs patients and may be implicated in generating a fibrotic microenvironment.", publisher = "Springer Nature", journal = "Advances in Molecular Pathology", booktitle = "Increase in Frequency of Myeloid-Derived Suppressor Cells in the Bone Marrow of Myeloproliferative Neoplasm: Potential Implications in Myelofibrosis", pages = "290-273", volume = "1408", doi = "10.1007/978-3-031-26163-3_15" }
Kapor, S., Momčilović, S., Kapor, S., Mojsilović, S., Radojković, M., Apostolović, M., Filipović, B., Gotić, M., Čokić, V., Santibanez, J. F.,& Simon, F.. (2023). Increase in Frequency of Myeloid-Derived Suppressor Cells in the Bone Marrow of Myeloproliferative Neoplasm: Potential Implications in Myelofibrosis. in Advances in Molecular Pathology Springer Nature., 1408, 273-290. https://doi.org/10.1007/978-3-031-26163-3_15
Kapor S, Momčilović S, Kapor S, Mojsilović S, Radojković M, Apostolović M, Filipović B, Gotić M, Čokić V, Santibanez JF, Simon F. Increase in Frequency of Myeloid-Derived Suppressor Cells in the Bone Marrow of Myeloproliferative Neoplasm: Potential Implications in Myelofibrosis. in Advances in Molecular Pathology. 2023;1408:273-290. doi:10.1007/978-3-031-26163-3_15 .
Kapor, Sunčica, Momčilović, Sanja, Kapor, Slobodan, Mojsilović, Slavko, Radojković, Milica, Apostolović, Milica, Filipović, Branka, Gotić, Mirjana, Čokić, Vladan, Santibanez, Juan F., Simon, Felipe, "Increase in Frequency of Myeloid-Derived Suppressor Cells in the Bone Marrow of Myeloproliferative Neoplasm: Potential Implications in Myelofibrosis" in Advances in Molecular Pathology, 1408 (2023):273-290, https://doi.org/10.1007/978-3-031-26163-3_15 . .