Transcriptome sequencing-based comparison of Myeloproliferative Neoplasms, with and without driver mutations, to identify molecular targets in triple-negative MPNs for precision therapy development
Implementing Organization
St. Johns Medical College, Bengaluru, Karnataka
Principal Investigator
Dr. sweta srivastava
St. Johns Medical College, Bengaluru, Karnataka
CO-Principal Investigator
Dr. seetharam Anandram
st John's Medical College And Hospital, Bengaluru, Karnataka-560034
CO-Principal Investigator
Dr. Lokendra Yadav
st John's Medical College And Hospital, Bengaluru, Karnataka-560034
CO-Principal Investigator
Dr. Hari Menon
st John's Medical College And Hospital, Bengaluru, Karnataka-560034
CO-Principal Investigator
Dr. Cecil R Ross
St. Johns Medical College, Bengaluru, Karnataka
About
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.