Th17 and non-Th17 interleukin-17-expressing cells in chronic lymphocytic leukemia: delineation, distribution, and clinical relevance

• Published in: Haematologica (Roma) Vol. 97; no. 4; pp. 599 - 607
• Main Authors: JAIN, Preetesh, JAVDAN, Mohammad, ROSENWALD, Andreas, ALLEN, Steven L, KOLITZ, Jonathan E, RAI, Kanti R, CHIORAZZI, Nicholas, SHERRY, Barbara, FEGER, Franziska K, PUI YAN CHIU, SISON, Cristina, DAMLE, Rajendra N, BHUIYA, Tawfiqul A, SEN, Filiz, ABRUZZO, Lynne V, BURGER, Jan A
• Format: Journal Article
• Language: English
• Published: Pavia Ferrata Storti Foundation 01-04-2012
• Subjects: Biological and medical sciences; Hematologic and hematopoietic diseases; Humans; Immunophenotyping; Interleukin-17 - metabolism; Leukemia, Lymphocytic, Chronic, B-Cell - immunology; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism; Leukemia, Lymphocytic, Chronic, B-Cell - mortality; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - pathology; Lymph Nodes - metabolism; Lymph Nodes - pathology; Lymphocyte Count; Medical sciences; Original and Brief Reports; Prognosis; Spleen - metabolism; Spleen - pathology; Survival Analysis; Th17 Cells - immunology; Th17 Cells - metabolism; Hematology; Helper cell; Malignant hemopathy; Microenvironment; Cell differentiation; Interleukin 17; Chronic lymphocytic leukemia; Lymphoproliferative syndrome; Distribution; T-Lymphocyte; IL-17; myeloid differentiation; Th17 lymphocyte; T lymphocyte; Th17; Cancer
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2011.047316

The levels and clinical relevance of Th17 cells and other interleukin-17-producing cells have not been analyzed in chronic lymphocytic leukemia. The objective of this study was to quantify blood and tissue levels of Th17 and other interleukin-17-producing cells in patients with this disease and correlate blood levels with clinical outcome.
Intracellular interleukin-17A was assessed in blood and splenic mononuclear cells from patients with chronic lymphocytic leukemia and healthy subjects using flow cytometry. Interleukin-17A-producing cells were analyzed in formalin-fixed, paraffin-embedded spleen and lymph node sections using immunohistochemistry and immunofluorescence.
The absolute numbers of Th17 cells in peripheral blood mononuclear cells and the percentages of Th17 cells in spleen cell suspensions were higher in patients with chronic lymphocytic leukemia than in healthy subjects; in six out of eight paired chronic lymphocytic leukemia blood and spleen sample comparisons, Th17 cells were enriched in spleen suspensions. Circulating Th17 levels correlated with better prognostic markers and longer overall survival of the patients. Two "non-Th17" interleukin-17-expressing cells were identified in chronic lymphocytic leukemia spleens: proliferating cells of the granulocytic lineage and mature mast cells. Granulocytes and mast cells in normal spleens did not express interleukin-17. Conversely, both chronic lymphocytic leukemia and healthy lymph nodes contained similar numbers of interleukin-17+ mast cells as well as Th17 cells.
Th17 cells are elevated in chronic lymphocytic leukemia patients with better prognostic markers and correlate with longer survival. Furthermore, non-Th17 interleukin-17A-expressing cells exist in chronic lymphocytic leukemia spleens as maturing granulocytes and mature mast cells, suggesting that the microenvironmental milieu in leukemic spleens promotes the recruitment and/or expansion of Th17 and other IL-17-expressing cells. The pathophysiology of Th17 and non-Th17-interleukin-producing cells in chronic lymphocytic leukemia and their distributions and roles in this disease merit further study.