ROLE OF ANKHD1 IN MULTIPLE MYELOMA PROGRESSION AND THERAPY

• Grant number: 12/10929-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2012
• End date: August 31, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Sara Teresinha Olalla Saad
• Grantee: Anamika Dhyani
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 11/51959-0 - Biology of neoplastic diseases of bone marrow, AP.TEM

Abstract

Multiple myeloma (MM) is the second most common hematologic malignancy worldwide and till date cure for multiple myeloma has not been achieved with chemotherapy alone. Thus, the development of new effective anti-cancer targets to treat both early and advanced MM seems to be an attractive perspective. One major step for development of the cancer therapeutics is to build a comprehensive molecular portrait of human cancer by characterizing actively expressed genes and the function of their coding proteins. Ankyrin repeat and KH domain-containing protein 1 (ANKHD1) is one such protein ubiquitously expressed in normal human tissues and has a varied and high expression in cancer, including acute leukemias. However its role in development of cancer is still unknown and is being investigated. Recently we showed that ANKHD1 is highly expressed in CD138+ cells from MM patients and MM cell lines MM1S, MM1R, U266 and RPMI 8226. Suppression of ANKHD1using lentiviral ANKHD1-shRNA vector potently inhibited proliferation and delayed cell cycle progression without affecting rate of apoptosis in MM cells. Hence in the present project we would like to investigate the underlying mechanism in ANKHD1 mediated proliferation and cell cycle progression. Data also suggest role of ANKHD1 in modulation of expression of cell cycle related genes such as CDKN1A (P21) and histones. So we would also investigate relation of ANKHD1 with p21 and histones. Further we would study efficacy of combined ANKHD1 silencing and chemotherapy in MM cells to develop effective therapeutic strategy.