Informations générales (source: ClinicalTrials.gov)
Natural Killer Cells Functions, Tumoral Escape to Immune System and Regulation of Natural Cytotoxixity Receptors in Haematological Malignancies
Interventional
N/A
Assistance Publique Hopitaux De Marseille (Voir sur ClinicalTrials)
février 2013
janvier 2015
29 juin 2024
The NK cells participate in the innate immunity against infectious agents or transformed
cells that are recognized as "no self" by the absent, weak or abnormal expression of
human leukocyte antigen (HLA) class I molecules. According to the "missing self
hypothesis", a negative signal is delivered to NK cells when their inhibitory receptors
are engaged by the specific HLA class I molecules. NK activation requires a positive
signal delivered by the engagement of activating receptors, more particularly of the
"Natural cytotoxicity receptors" or NCRs who are directly involved in the natural
cytotoxicity of Natural Killer. The activating receptors include NKp46, NKp44 and NKp30,
also called NCR 1, 2 and 3 respectively. NKp46 and NKp30 are constitutively expressed on
the surface of the NK, the expression of NKp44 is observed only after activation of cells
NK. NK cells from most (80%) healthy donors express a high quantity of NCR on their
surface, corresponding to the NCRbright phenotype while only 20 % present the NCRdull
phenotype. In sharp contrast, most patients (80%) having leukaemia have the NCRdull while
only 20 % patients have the NCRbright phenotype. The culture of NK from healthy donors (
NCRbright) with leukaemic cells result in decreased expression of the NKp30 while there
is no difference on expression if these same NK are cultivated with cells from healthy
donors. Moreover, study of AML patients showed that the NCRdull phenotype was acquired
during leukemia development because it was observed its complete (for NKp46) or partial
(for NKp30) reversibility in patients achieving complete remission (CR). Reversibility of
the NCRdull phenotype after CR suggested that leukemia cells might be involved in NCR
down-regulation. In line with these observations, we aim to study the mechanism of NCR
down-regulation by cultivating NK NCRbright from healthy donors with leukaemic cells or
healthy haematopoietic cells, in order to observe the appearance of the NCRdull phenotype
and verify by qPCR if this down-regulation is transcriptionnal. If this hypothesis is be
verified, we will study the regulation of NCR by focusing on the implication of genes NCR
transcription factors via bio-informatic analysis of putative transcription factors
fixation sequences in the promoters of these genes, followed by the verification of the
capacity of identified sequences to bind transcription factors. Ultimately, we will
verify the real implications of these transcription factors by studying the effect of
their silencing by RNA interference experiments.
Etablissements
| Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| Assistance Publique Hopitaux de Marseille - 13354 - Marseille - France | laure farnault | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
- Grown-up patients having a leukaemia aigue myéloïde (LAM) in the diagnosis, whatever
is LAM's subcategory (FAB or cytogenetics).
- The patients that must be informed at the same time, willing, and having given their
agreement in writing.
- Grown-up patients having a leukaemia aigue myéloïde (LAM) in the diagnosis, whatever
is LAM's subcategory (FAB or cytogenetics).
- The patients that must be informed at the same time, willing, and having given their
agreement in writing.
- Refusal of the patient.
- Phénotypage NK not corresponding to the quotas dull / bright required.