Characterization of two novel cell lines, DERL-2 (CD56+/CD3+/TCRγδ+) and DERL-7 (CD56+/CD3−/TCRγδ−), derived from a single patient with CD56+ non-Hodgkin's lymphoma

Abstract

Two novel IL2-dependent cell lines, DERL-2 and DERL-7, were established from a patient with hepatosplenic gammadelta T cell lymphoma. This patient presented, at diagnosis, two discrete populations of CD56+ cells, one TCRgammadelta+, the second lacking T cell-restricted antigens. The cell lines derived displayed features corresponding to the two cellular components of the disease: DERL-2 was CD56+/CD3+/TcRgammadelta+ while DERL-7 was CD56+/CD3-/TcRgammadelta-. Along with CD56, the two cell lines shared the expression of CD7, CD2, CD158b and CD117. Karyotype analysis showed that both cell lines were near-diploid, with iso-7q and loss of one chromosome 10. In addition, DERL-2 showed 5q+ in all metaphases analyzed, while DERL-7 revealed loss of one chromosome 4. Genotypically, both cell lines shared the same STR pattern at nine loci and demonstrated an identical rearranged pattern of the T cell receptor genes beta, gamma and delta, with respect to the original tumor cells. These data indicated that both cell lines and the original neoplastic populations were T cell-derived and arose from a common ancestor. Among a large panel of cytokines tested, only SCF was able to substitute IL2 in supporting cell proliferation. Moreover, SCF and IL2 acted synergistically, dramatically enhancing cell growth. These cell lines may represent a model to further analyze the overlap area between T and NK cell malignancies, and may provide new information about the synergistic action of IL2 and SCF on normal and neoplastic T/NK cells.

NKp46 identifies an NKT cell subset susceptible to leukemic transformation in mouse and human

“…Consistent with this report is the finding that many if not all human cell lines that are derived from NK or T-LGL leukemias are in fact dependent on exogenous IL-15 or IL-2 stimulation, both of which work through the IL-2/15Rβγ signaling components (50)(51)(52). This would suggest that other cells, such as DCs or stromal cells, may have deregulated IL15 gene expression, which leads to malignant conversion of the NKp46 + LGL in vivo.…”

Molecular features of hepatosplenic T-cell lymphoma unravels potential novel therapeutic targets

“…Normal ␥␦ T cells sorted using a magnetic anti-TCR␥/␦ microbeads kit (Miltenyi Biotec) from 3 spleens removed for benign conditions were also obtained for quantitative RT-PCR (qRT-PCR) validation. DERL2, a ␥␦ cell line derived from HSTL, 22 was cultured in IMDM supplemented with 2mM L-glutamine and 20% heatinactivated human serum (Invitrogen) in the presence of recombinant human IL-2 (100 U/mL; Laboratoires Chiron). Centrifuged pellets of DERL2 cells were fixed in ethanol to construct paraffin-embedded blocks.…”

Stem cell factor and interleukin-2/15 combine to enhance MAPK-mediated proliferation of human natural killer cells

“…The IL-2-dependent CD3 Ϫ CD56 ϩ NK-cell line DERL-7 12 (a generous gift from R. Di Noto and CEINGE Biotechnologie, Naples, Italy) was maintained in RPMI 1640 (Invitrogen, Carlsbad, CA) supplemented with 20% FCS (Invitrogen), antibiotics (Invitrogen), and 150 IU/mL IL-2 (Hoffman-LaRoche, Nutley, NJ). The NK-cell line DERL-7 has been shown to be phenotypically and functionally similar to the human CD56 bright subset.…”

“…The NK-cell line DERL-7 has been shown to be phenotypically and functionally similar to the human CD56 bright subset. 12 The major functional difference between the cell line and primary human NK cells is that the DERL-7 line exhibits a modest proliferative response to SCF alone, whereas this effect is not seen in primary human NK cells.…”