Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated whether minor histocompatibility (mH) antigen-specific cytotoxic T lymphocytes (CTL) can discriminate between leukemic hematopoietic progenitor cells (leukemic-HPC) from AML or CML patients, the HPC from their remission bone marrow (remission-HPC), and normal HPC from their HLA-identical sibling bone marrow donor (donor-HPC). Specific lysis by CD8+ CTL clones was observed not only of the leukemic-HPC but also of the donor-HPC in 3/4 patient/donor combinations expressing mH antigen HA-1, 3/5 combinations expressing mH antigen HA-2, 2/3 combinations expressing mH antigen HA-3, and 2/2 combinations expressing mH antigen HY-A1. In four patient/donor combinations the recognition of the donor-HPC was clearly less than of the leukemic-HPC, indicating differential susceptibility to lysis by these mH CTL clones. In addition, differential recognition of leukemic-HPC and remission-HPC within seven patients was analyzed. In one patient expressing the HA-2 antigen on the leukemic cells the recognition of the remission-HPC was clearly less than of the leukemic-HPC. One CD4+ CTL clone showed specific lysis of the leukemic-HPC from an AML patient and a CML patient as well as of normal remission-HPC and donor-HPC. These results illustrate that in general CD8+ and CD4+ mH antigen specific CTL clones do not differentially recognize leukemic-HPC and normal-HPC. However, differences in susceptibility to lysis of malignant versus normal cells may contribute to a differential GVL effect.
 ...
PMID:Recognition of clonogenic leukemic cells, remission bone marrow and HLA-identical donor bone marrow by CD8+ or CD4+ minor histocompatibility antigen-specific cytotoxic T lymphocytes. 763 82

Acute lymphoblastic leukaemia (ALL) responds well to chemotherapy and the majority of children and a significant proportion of adults are cured of their disease after primary therapy. However, a number of patients relapse and allogeneic transplantation following conditioning with chemotherapy and radiotherapy offers the possibility of long-term survival in a proportion of these patients. A significant number of patients with ALL develop disease that is refractory to further therapy. The infusion of unmodified donor lymphocytes (DLI) following relapse after allogeneic transplantation has been shown to be curative in patients with chronic myeloid leukaemia (CML). However, in ALL the success rate is much lower. The results of in vitro and limited in vivo studies suggest that it may be possible to manipulate lymphocytes from the transplant donor to produce cytotoxic T-lymphocytes (CTL) with increased effectiveness in killing patients' ALL cells. This may be done in a number of ways. For example, some strategies utilise the patients dendritic cells (DC) to present tumour antigens to donor lymphocytes and convert them into CTL either by pulsing DC taken in remission with ALL cells or lysate, fusing such 'normal' DC with ALL cells or using DC cultured from the patient's ALL cells. Other approaches include exploiting the expression of leukaemia-specific antigens such as the proteinase PR-3 or the zinc finger transcription factor Wilms tumour-1 protein (WT-1) to stimulate CTL responses. Alternatively, immunotherapeutic strategies might exploit differences in minor histocompatibility antigens such as HA-1 and HA-2 between donor and recipient. These are expressed solely on haemopoietic cells making them suitable targets for donor derived anti-leukaemic cells. In vivo studies to date suggest that educated T-cells may have a role to play in the treatment of relapsed and refractory ALL in the future.
 ...
PMID:Immunotherapeutic strategies in acute lymphoblastic leukaemia relapsing after stem cell transplantation. 1627 19