Life Sciences & Biotechnology
Title : | Epigenetic vulnerabilities associated with loss of PHF6 in Acute Myeloid Leukemia |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Mayukh Biswas, Presidency University, Kolkata, West Bengal |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | mayukhbiswas.89@gmail.com |
Equipments : | Liquid Nitrogen sample storage cryovial store Haier Biomedical YDs-65-216-F LN2 capacity 65L, racks
Mini PROTEAN® Tetra Cell, Mini Trans Blot® Module, and PowerPac⢠Basic Power supply and Mini-sub Cel |
Details
Executive Summary : | AML is a disease characterized by abnormal proliferation and differentiation of a clonal population of stem cells, which are restricted to myeloid lineage. These stem cells can sustain hematopoiesis long term, but mutational events can alter their self-renewal, leading to the development of leukemia. somatic mutations in Plant Homeodomain Factor 6 (PHF6) are highly recurrent in human leukemias with T cell and myeloid phenotypes, with PHF6 mutations found in 3.2% of de novo AML, 3% MDs, 4.7% CMML, and 1.6% CML patients. Two-thirds of these mutations are frameshift and nonsense mutations, resulting in the loss of PHF6 protein. PHF6 loss is also found in patients with preleukemic clonal hematopoiesis, supporting a role for this tumor suppressor in leukemia initiation and HsC function. The specific molecular mechanisms by which PHF6 governs stem cell activity and its functional role in leukemia, particularly the mechanism by which PHF6 mutations accelerate AML transformation, remain to be elucidated. This study aims to dissect the cellular composition, structure, and function of PHF6 in complex with chromatin organization factors involved in epigenetic regulation of leukemia tumor suppressor and hematopoietic stem cell homeostasis programs using proteomics and epigenetic profiling analyses. The study will investigate the interaction of PHF6 with other key genes implicated in gene expression control and identify selective vulnerabilities resulting from PHF6 loss in leukemia initiating cells. |
Total Budget (INR): | 27,27,980 |
Organizations involved