Bone Marrow Soluble Mediator Signatures of Patients With Philadelphia Chromosome-Negative Myeloproliferative Neoplasms

Author(s):Show less -

Cominal, Jucara Gastaldi ^{[1, 2]} ; Cacemiro, Maira da Costa ^{[1, 2]} ; Berzoti-Coelho, Maria Gabriela ^{[1, 2]} ; Pereira, Illy Enne Gomes ^{[1, 2]} ; Frantz, Fabiani Gai ^[1] ; Souto, Elizabeth Xisto ^[3] ; Covas, Dimas Tadeu ^[2] ; Figueiredo-Pontes, Lorena Lobo de ^{[2, 4]} ; Oliveira, Maria Carolina ^{[2, 5]} ; Malmegrim, Kelen Cristina Ribeiro ^{[1, 2]} ; Castro, Fabiola Attie de ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, Ribeirao Preto - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Reg Blood Ctr, Ctr Cell Based Therapy, Ribeirao Preto - Brazil

^[3] Euryclides de Jesus Zerbini Transplant Hosp, Dept Clin Hematol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med Imaging Hematol & Clin Oncol, Div Hematol Hemotherapy & Cellular Therapy, Ribeirao Preto - Brazil

^[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Div Rheumatol Allergy & Immunotherapy, Ribeirao Preto - Brazil

• Document type: Journal article
• Source: FRONTIERS IN ONCOLOGY; v. 11, MAY 18 2021.
• Web of Science Citations: 0

Abstract

Background Essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) are clonal hematological diseases classified as Philadelphia chromosome-negative myeloproliferative neoplasms (MPN). MPN pathogenesis is associated with the presence of somatic driver mutations, bone marrow (BM) niche alterations, and tumor inflammatory status. The relevance of soluble mediators in the pathogenesis of MPN led us to analyze the levels of cytokines, chemokines, and growth factors related to inflammation, angiogenesis and hematopoiesis regulation in the BM niche of MPN patients. Methods Soluble mediator levels in BM plasma samples from 17 healthy subjects, 28 ET, 19 PV, and 16 PMF patients were determined using a multiplex assay. Soluble mediator signatures were created from categorical analyses of high mediator producers. Soluble mediator connections and the correlation between plasma levels and clinic-laboratory parameters were also analyzed. Results The soluble mediator signatures of the BM niche of PV patients revealed a highly inflammatory and pro-angiogenic milieu, with increased levels of chemokines (CCL2, CCL5, CXCL8, CXCL12, CXCL10), and growth factors (GM-CSF M-CSF, HGF, IFN-gamma, IL-1 beta, IL-6Ra, IL-12, IL-17, IL-18, TNF-alpha, VEGF, and VEGF-R2). ET and PMF patients presented intermediate inflammatory and pro-angiogenic profiles. Deregulation of soluble mediators was associated with some clinic-laboratory parameters of MPN patients, including vascular events, treatment status, risk stratification of disease, hemoglobin concentration, hematocrit, and red blood cell count. Conclusions Each MPN subtype exhibits a distinct soluble mediator signature. Deregulated production of BM soluble mediators may contribute to MPN pathogenesis and BM niche modification, provides pro-tumor stimuli, and is a potential target for future therapies. (AU)

• FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
• Grantee: Dimas Tadeu Covas
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 14/50947-7 - INCT 2014: in Stem Cell and Cell Therapy
• Grantee: Dimas Tadeu Covas
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/01756-5 - Immunological and Functional Characterization of Multipotent Mesenchymal Stromal Cells in Myeloproliferative Neoplasms
• Grantee: Maira da Costa Cacemiro
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/19714-7 - Bone Marrow Mesenchymal Stromal Cells deregulation effect on BCR-ABL1-Myeloproliferative Neoplasms pathophysiology and progression
• Grantee: Fabíola Attié de Castro
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/23555-3 - Regulators microRNAs of HIPPO pathway in Chronic Myeloid Leukemia
• Grantee: Maria Gabriela Berzoti Coelho
• Support Opportunities: Scholarships in Brazil - Doctorate