Expression of Cytokine mRNA in Leukemic Cells from Adult T Cell Leukemia Patients

Abstract

HTLV‐I infection of peripheral mature T cells appears to induce the expression of cellular genes including those of some cytokines and their receptors. We examined the expression of interleukin‐lα (IL‐lα), IL‐lβ, IL‐2, IL‐3, IL‐4 and granulocyte/macrophage colony‐stimulating factor (GM‐CSF) at the mRNA level in fresh leukemic cells from 20 adult T cell leukemia patients to see whether there is any association between cytokine expression and MTLV‐I expression and between their expression and clinical manifestations such as hypercalcemia or neutrophilia. IL‐lα, IL‐Iβ and IL‐3 expression was observed in 3, 7 and 1 of 20 cases examined, respectively. However, there seemed to be no association between IL‐1 expression and clinical manifestations. IL‐2, IL‐4 and GM‐CSF mRNA expression was not detected. HTLV‐I viral RNA expression was detected only in one case in which IL‐3 mRNA was expressed in both peripheral blood and lymph node cells and a relatively high proportion of leukemic cells expressed IL‐2 receptor (p55, Tac). Thus, in the present study we could not find any correlation between cytokine expression and HTLV‐I expression in peripheral blood fresh leukemic cells except in one unusual case.

Cytokine induction in HTLV‐I associated myelopathy and adult T‐cell leukemia: Alternate molecular mechanisms underlying retroviral pathogenesis

“…Furthermore, TNF-a can induce the production of IL-1P in vitro [41]. [42] we also observed IL-1P mRNA expression in the PBMC of some ATL patients. However, consistent with the previous studies there was no association between IL-lP expression and clinical hypercalcemia.…”

Rapid tumor formation and development of neutrophilia and splenomegaly in nude mice transplanted with human cells expressing human T cell leukemia virus type I or Tax1

“…In ATL patients, splenomegaly and neutrophilia are typical signs of this disease: neutrophil counts significantly increase as compared to patients with acute lymphoblastic leukemia or non-Hodgkin's lymphoma, or those of normal persons. 47,48 Splenomegaly, neutrophilia and neutrophil invasion into tumor tissues probably due to production of mGM-CSF from neurofibroma or LGL leukemia cells were reported in tax1-transgenic mice as described above. 42,44 In contrast, we observed high levels of G-CSF in sera of mice with neutrophilia and splenomegaly (Table 3), while G-CSF was not detected (Ͻ7 pg/ml) in mice with normal neutrophil counts.…”

Expression of alternatively spliced human T-lymphotropic virus type I pX mRNA in infected cell lines and in primary uncultured cells from patients with adult T-cell leukemia/lymphoma and healthy carriers.

“…The tax gene can also transform NIH 3T3 and Rat-i fibroblasts (6). Previous studies have failed to readily detect HTLV-I antigens (7)(8)(9) and mRNA (10)(11)(12) in the leukemic cells of ATL patients, suggesting that HTLV-I gene expression is not required for the progression to and maintenance of the leukemic state and that the role of the virus may be limited to the induction of polyclonal T-lymphocyte proliferation years to decades before the development of ATL. This proliferation could lead to secondary events, increasing the chance for leukemia, at which stage HTLV-I gene expression would not be necessary (13).…”