Philadelphia-negative myeloproliferative neoplasms display alterations in monocyte subpopulations frequency and immunophenotype

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Bassan, Vitor Leonardo ; Barretto, Gabriel Dessotti ; de Almeida, Felipe Campos ; Bonini Palma, Patricia Vianna ; Binelli, Larissa Sarri ; Lettieri da Silva, Joao Paulo ; Fontanari, Caroline ; Castro, Ricardo Cardoso ; de Figueiredo Pontes, Lorena Lobo ; Frantz, Fabiani Gai ; de Castro, Fabiola Attie

• Document type: Journal article
• Source: MEDICAL ONCOLOGY; v. 39, n. 12, p. 12-pg., 2022-09-29.

Abstract

Philadelphia-negative myeloproliferative neoplasms (MPN) are clonal hematological diseases associated with driver mutations in JAK2, CALR, and MPL genes. Moreover, several evidence suggests that chronic inflammation and alterations in stromal and immune cells may contribute to MPN's pathophysiology. We evaluated the frequency and the immunophenotype of peripheral blood monocyte subpopulations in patients with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (MF). Peripheral blood monocytes from PV (n = 16), ET (n = 16), and MF (n = 15) patients and healthy donors (n = 10) were isolated and submitted to immunophenotyping to determine the frequency of monocyte subpopulations and surface markers expression density. Plasma samples were used to measure the levels of soluble CD163, a biomarker of monocyte activity. PV, ET, and MF patients presented increased frequency of intermediate and non-classical monocytes and reduced frequency of classical monocytes compared to controls. Positivity for JAK2 mutation was significantly associated with the percentage of intermediate monocytes. PV, ET, and MF patients presented high-activated monocytes, evidenced by higher HLA-DR expression and increased soluble CD163 levels. The three MPN categories presented increased frequency of CD56(+) aberrant monocytes, and PV and ET patients presented reduced frequency of CD80/86(+) monocytes. Therefore, alterations in monocyte subpopulations frequency and surface markers expression pattern may contribute to oncoinflammation and may be associated with the pathophysiology of MPN. (AU)

• 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: 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: 19/18013-8 - Immunophenotypic and molecular characterization of monocyte subpopulations in myeloproliferative neoplasms
• Grantee: Vitor Leonardo Bassan
• Support Opportunities: Scholarships in Brazil - Master