Research

Life Sciences & Biotechnology

Title :

Transcriptome sequencing-based comparison of Myeloproliferative Neoplasms, with and without driver mutations, to identify molecular targets in triple-negative MPNs for precision therapy development

Area of research :

Life Sciences & Biotechnology

Principal Investigator :

Dr. sweta srivastava, st. John's Medical College, Bengaluru, Karnataka

Timeline Start Year :

2023

Timeline End Year :

2026

Contact info :

Details

Executive Summary :

Myeloproliferative neoplasms are hematological disorders due to mutation in JAK2, CALR, or MPL genes. These mutations drive approximately 30% of the MPN cases and the hazard ratio of death is 92.8 (95% CI, 70.0 to 123.1) from MPN as compared to 2.7 (95% CI, 2.4 to 3.1) with infections. A subset of the MPN (triple-negative) does not exhibit driver mutations associated with the disease progression and thus there is no identified target that can be used for treatment, unlike JAk2 positive MPNs wherein Jakafi can be used. Thus, there is a need to identify novel molecular targets for this subset of MPNs. Identification of unique molecular targets in this subset will help in the development of targeted therapy and thus this proposal aims to conduct a transcriptomic study on the MPN samples (both mutant positive and negative) to identify new targets. De-novo RNA sequencing will be done on the peripheral blood mononuclear cells from MPN patients without driver mutations and will be compared with the transcriptome of MPNs with driver mutations. The expected outcome of the project is the identification of a novel signaling target for precision therapy development and biomarker development for disease stratification. It will also provide an understanding of the biology of disease progression in triple-negative MPNs.

Co-PI:

Dr. Cecil R Ross, st. Johns Medical College, Bengaluru, Karnataka-560034, Dr. seetharam Anandram, st John's Medical College And Hospital, Bengaluru, Karnataka-560034, Dr. Lokendra Yadav, st John's Medical College And Hospital, Bengaluru, Karnataka-560034, Dr. Hari Menon, st John's Medical College And Hospital, Bengaluru, Karnataka-560034

Total Budget (INR):

58,88,360

Organizations involved