Background and Aims

We recently reported that graft-versus-leukemia (GVL) effect was observed in acute lymphocytic leukemia (ALL) with TCF3-PBX1 (53rd ASH, and 15th ASGCT). To understand better the mechanism of this GVL effect, we analyzed blood T cell receptors (TCRs) obtained from ALL patients with TCF3-PBX1.

Materials and Methods

The institutional ethical committee approved our study using clinical materials. Three informed ALL patients with TCF3-PBX1 were eligible. Leukemic blasts, blood lymphocytes after underwent allogeneic hematopoietic stem cell transplantation to achieve and keep complete remission, and cells from pathologically GVHD-diagnosed organs (liver, and skin) were collected. Lymphocytes were co-cultured with the patient-derived ALL blasts that were priory irradiated at 20 Gray (GVL model) or GVHD-related cells (GVHD model) for 14 days with recombinant human interleukin-2. Then, TCR Valpha (Va) and Vbeta (Vb) usages were analyzed with RT-PCR. When the preferential usage of Va and Vb was observed, T cells underwent single-cell culture, and the clones showing ALL blast-killing activity and not GVHD effect were selected, and their TCR nucleotide sequences were analyzed.

Results

In GVHD model and GVL one, TCR Va and Vb were oligoclonally used, in which Vb 6, 10, and 14 were preferentially used in GVL model but not in GVHD. On Va no selective usage was demonstrated between GVL model and GVHD one. Furthermore, the obtained single cells with GVL effect had specific TCR Vb nucleotide-sequences.

Discussion

In GVL model TCR Vbs were preferentially used. Currently we isolate tcf3-pbx1-specific oligopeptide-antigen recognized by the isolated TCRs, and observe cytotoxic GVL effect with the isolated TCRs in vitro. We also validate in vivo implications of the isolated GVL-specific T cells to treat leukemic non-obese diabetes/severe combined immunodeficiency mouse generated by the injection of ALL-blast with TCF3-PBX1.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
acute lymphocytic leukemia, leukemia, t-cell receptor, tcf3 gene, tissue transplants, obesity, graft-versus-host disease, aldesleukin, allogeneic hematopoietic stem cell transplant, antigens

Author notes

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Asterisk with author names denotes non-ASH members.

© 2013 by The American Society of Hematology
2013
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