MM accounts for 10% of hematopoietic malignancies. Despite the use of various drug combinations in chemotherapy, life expectancy of MM patients does not exceed 7 years. Until now, lack of specific markers of the disease has not allowed efficient specific molecular targeting. In view of our preliminary results, the antiapoptotic protein Bcl-B could be a novel diagnostic and pronostic marker of MM. Therefore, our main objective will be to confirm that Bcl-B is indeed a novel diagnostic and pronostic marker and a new potential therapeutic target of MM. Targeting Bcl-2 family member's is a promising strategy for the treatment of hematopoietic malignancies. In this context, specific targeting of Bcl-B could improve the treatment of patients suffering MM. Of note, this could be achieved by converting the antiapoptotic function of Bcl-B to a proapoptotic one thanks to the use of small mimetic peptides derived from Nur77 one of its interactors.
Study Type
OBSERVATIONAL
Enrollment
60
Service de Médecine interne et cancérologie - Hôpital de l'Archet
Nice, France
To determine whether BCL-B is a survival factor in malignant plasmocytes, we will analyse the level of expression of Bcl-B at the both mRNA and protein levels in a cohort of MGUS and MM patients.
To determine whether BCL-B is a survival factor in malignant plasmocytes,we will analyse the level of expression of Bcl-B at the both mRNA and protein levels in a cohort of MGUS and MM patients. The implication of Bcl-B in malignant plasmocyte survival will be evaluated by loss of fucntion experiments (Si-RNA). This will also allow to determine whether Bcl-B is involved in the MGUS to MM transition.
Time frame: 6 months
To determine whether deregulation of BCL-B expression is associated to chimioresistances commonly observed in Multiple Myeloma, We will compare Bcl-B expression in MM patients either sensitive or resistant to conventional therapies.
To determine whether deregulation of BCL-B expression is associated to chimioresistances commonly observed in Multiple Myeloma, We will compare Bcl-B expression in MM patients either sensitive or resistant to conventional therapies. We will focuse on resistance to Velcade. we have also isolated established MM cell lines resistant to velcade in vitro which will be useful for the study with MM patients samples.
Time frame: 6 months
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