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Janus kinase 3 inhibitor WHI-P131/JANEX-1 prevents graft-versus-host disease but spares the graft-versus-leukemia function of the bone marrow allografts in a murine bone marrow transplantation model.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Uckun, Fatih M. Roers, Bertram A. Waurzyniak, Barbara Liu, Xing-Ping Cetkovic-Cvrlje, Marina |
| Copyright Year | 2002 |
| Abstract | The purpose of the present study was to evaluate the effects of graft-versus-host disease (GVHD) prophylaxis with the Janus kinase 3 (JAK3) inhibitor WHI-P131/JANEX-1 on the graft-versus-leukemic (GVL) function of marrow allografts in mice undergoing bone marrow transplantation (BMT) after being challenged with an otherwise invariably fatal dose of BCL-1 leukemia cells. GVHD prophylaxis using WHI-P131 markedly improved the survival outcome after BMT. The probability of survival at 30 days after BMT was 11% +/- 6% for vehicle-treated recipients (median survival time, 25 days) versus 63% +/- 12% for recipients treated with WHI-P131 (median survival time, 36 days; P <.0001). Because WHI-P131 is devoid of antileukemic activity against BCL-1 leukemia cells, this marked improvement in survival outcome was due to reduced incidence of GVHD-associated fatalities combined with sustained GVL function of the allografts in the WHI-P131 group. Notably, adoptive transfer experiments demonstrated that the spleens of WHI-P131-treated allograft recipients contained less than 0.001% BCL-1 cells. Notably, GVHD prophylaxis with WHI-P131 plus methotrexate resulted in 100% survival of mice receiving allotransplants challenged with an otherwise invariably fatal dose of BCL-1 leukemia. Taken together, our results provide strong experimental evidence that GVHD prophylaxis using WHI-P131 does not impair the GVL function of the allografts and consequently contributes to an improved post-BMT survival outcome of the recipient mice. |
| Starting Page | 23 |
| Ending Page | 31 |
| Page Count | 9 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.bloodjournal.org/content/bloodjournal/99/11/4192.full.pdf?sso-checked=true |
| PubMed reference number | 12010825v1 |
| Volume Number | 99 |
| Issue Number | 11 |
| Journal | Blood |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Allograft surgical material Bone Marrow Transplantation Contain (action) Graft versus host disease prophylaxis/therapy Graft vs Leukemia Effect Leukemia, B-Cell Methotrexate Spleen Transplantation, Homologous Transplanted tissue WHI P131 Women's Health Initiative (WHI) |
| Content Type | Text |
| Resource Type | Article |
