Authors |
Kadin M.E., Cavaille-Col M.W., Sioutos N., Fletcher J.A., Morton C.C., Pastuzak W., Rezuke W., Altman A.J. |
Abstract |
Ki-1 anaplastic large cell lymphoma (ALCL) is a newly recognized
clinicopathologic entity characterized by a distinctive chromosome
translocation, t(2;5)(p23;q35), sinus and paracortical infiltration of
lymph nodes, frequent extra-nodal disease (especially skin, soft tissue,
CI tract and bone), and expression of lymphocyte activation antigens
(CD3O, CD25, transferrin receptor, and HLA-DR) by pleomorphic tumor cells.
Spontaneous regression of skin lesions is frequently encountered. The peak
age incidence of ALCL is childhood and adolescence. A good response to
chemotherapy (COMP or D-COMP) with an excellent event-free survival has
been reported for most patients with ALCL; however a subset of patients
have treatment resistant disease. To better understand the biology of ALCL
and to develop new approaches to therapy, we established a cell line from
leukemic cells of a 12 year old boy (JB) with treatment resistant disease.
The morphology of JB cells consists of a spectrum of small Sezary-like
cells and larger immunoblasts including multinucleated Reed-Sternberg like
cells. The immunophenotype is that of an activated T-cell: positive for
CD2, CD7, Bfl, CD30, CD25, transferrin receptor, CD45, HLA-DR and for the
histiocyte-macrophage marker KP-1. JB cells have the t(2;5) and clonal
rearrangement of beta chain T-cell receptor genes but germline
configuration of immunoglobulin JH gene. The cloning efficiency is 5% and
the doubling time is 60 hr in methylcellulose with IMDM and 15% FCS. JB
cells were injected intraperitoneally to form a metastasizing tumor in
SCID mice. The transplanted tumor maintains the original morphology,
immunophenotype and genotype. Tumor fragments have been passaged
repeatedly subcutaneously reaching a tumor size of greater than 1 cm in
4-6 weeks. The subcutaneous tumors remain outside the abdominal wall fascia
and do not metastasize. Preliminary experiments of tumor directed therapy
have been initiated. This cell line should provide a means of designing
more effective therapies for treatment-resistant Ki-1 + ALCL.
|