Mastocytosis: from physiopathology to treatment

Speaker:
Dr Michel Arock
Professor of Physiology and Hematology
Laboratoire de Biologie et Pharmacologie Appliquée (ENS Cachan)and Clinical Laboratory of Hematology
(Hôpital de la Pitié-Salpêtrière, Paris)

Host:
Prof Soman Abraham
Program in Emerging Infectious Diseases
Duke-NUS Graduate Medical School

Date:
Thursday , 7 June 2012

Time:
11.00 AM — 12.00 PM

Venue:

Conference 4D, Level 4
Duke-NUS Graduate Medical School
8 College Road, Singapore 169857
(opposite Singapore General Hospital, Block 6/7)

Contact Person:

Serene Chee, Administrative Assistant

Emerging Infectious Diseases Program

Tel; 660 11488    Email: serene.chee@duke-nus.edu.sg

Synopsis:

Mastocytosis is a myeloid neoplasm characterized by abnormal accumulation and frequent activation of mast cells (MCs) in various organs. Organ systems typically involved are the bone marrow, skin, liver and gastrointestinal tract. In most adult patients, the systemic form of mastocytosis (SM) is diagnosed, which includes an indolent subvariant, an aggressive subvariant and a leukemic subvariant, also termed MC leukemia.

Whereas in pediatric mastocytosis, which is usually confined to the skin, a number of different KIT mutations and other defects may be detected, the KIT mutation D816V is detectable in most (adult) patients with SM. In a subset of these patients, additional oncogenic factors may lead to enhanced survival and growth of MCs and, thus, to advanced SM.

Treatment of SM usually focuses on symptom relief by histamine receptor antagonists and other supportive therapy. However, in aggressive and leukemic variants, cytoreductive and targeted drugs must be applied. Unfortunately, the prognosis in these patients remains poor, even when treated with novel KIT-targeting agents, due to rapid appearance of resistance. For this reason, one might consider targeting other signaling molecules such as STAT-5, Fes, Hsp32, mTOR, JNK, Hsp90, MCL-1, Lyn, Btk, etcrock  and to use these targeted drugs in combination in order to overcome KIT D816V resistance.

Biography:

Biography: Michel Arock is Doctor in Pharmacy of the University René Descartes of Paris (1982) and has obtained a 4 years full specialization in Medical Biology at the AP-HP (Assistance Publique-Hôpitaux de Paris) in 1986. He has obtained his PhD (specialty: Hematology) always at the University René Descartes of Paris in 1988 with researches focused on the mechanisms of human mast cell differentiation from hematopoietic progenitors. Since 2002, he is head of the Emergency Laboratory of Clinical Biology at la Pitié-Salpêtrière Hospital in Paris, which takes in charge the monitoring of all biological parameters (Hematology and Hemostasis, Biochemistry and Blood Gas) for all the patients in resuscitation or emergency units and in operative rooms. Besides, since 2005, he is Full Professor in Human Physiology and Hematology at the Department of Biology (LBPA CNRS UMR 8113) of the Ecole Normale Supérieure de Cachan, where he leads a research team working on Human Mast cell Biology as well as on the Pathophysiology of mastocytosis. He is the French correspondent of the European Competence Network on Mastocytosis (ECNM: http://ecnm.net/homepage/index.php) and Vice-President of the French association of mastocytosis patients (AFIRMM: http://www.afirmm.com/index_default.php). He has coauthored more than 120 articles or book chapters, mostly focused on the mechanisms underlying differentiation and activation of human mast cells and basophils, as well as on the Pathophysiology of mastocytosis.