To identify novel therapeutic targets and diagnostic markers for ATL, we employed focused proteomic profiling of the CD4(+)CD25(+)CCR4(+) T-cell subpopulation in which HTLV-1-infected cells were enriched.
In the present study, we show that an IκB kinase 2 (IKK2) inhibitor, IMD-0354, efficiently inhibits the survival of CD4(+) CD25(+) primary ATL cells and prevents the growth of or induces apoptosis of patient-derived ATL cell lines.
In this study, we preliminarily investigated the mechanism of internalization of CCR9 on MOLT4 cell model (a human leukemia T-cell line, naturally expresses CCR9) and found that IL-2 upregulated the cell surface expression of IL-4Ralpha (CD124) greatly, whereas IL-4 had no significant influence on alpha (CD25) and beta subunits (CD122) of IL-2R.
Leukemic (ATL) T cells constitutively expressing CD25 were characteristic of heterogeneous Foxp3 expression, such as intra- and inter-case heterogeneity in intensity, inconsistency with CD25 expression, and a discrepancy in the mRNA and its protein expression.
Flow cytometry indicated a (CD25(+)/CD7(-)) T-cell lineage, suggesting an human T-lymphotropic virus (HTLV) 1-related T-cell leukemia/lymphoma, which was confirmed by polymerase chain reaction (PCR)-based amplification on DNA extracted from fresh tissue with specific oligonucleotide primers for HTLV-1 DNA sequence.
The surface phenotype showed that both the original leukemic cells and the WHN2 cells had a common phenotype of ATL, i.e., positive for CD2, CD4, human leukocyte antigen DR (HLA-DR) and CD25, but negative for CD8, a characteristic of helper/inducer T-cells.
The tumor cells represented outgrowth of the original ATL leukemic clone in that they had monoclonal or oligoclonal integrations of the HTLV-I provirus identical to the leukemic clone and predominantly expressed the cell surface markers, CD4 and CD25.
Adult T-cell leukemia (ATL) cells have been shown to express the receptor for IL-2 by studies using anti-CD25 monoclonal antibody, but these cells usually show no or only a weak proliferative response to IL-2.