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Role of the g-protein-coupled receptor p2ry14 in acute leukemia

Shah, Kinjal (2017) MOBT01 20161
Degree Projects in Molecular Biology
Popular Abstract
Leukemia involves uncontrolled proliferation of different types of blood cells. Accordingly, it is classified as Acute myeloid leukemia (AML), Acute lymphoblastic leukemia (ALL; which includes B cell and T cell – ALL), Chronic myeloid leukemia (CML) and Chronic lymphoblastic leukemia (CLL). Children are more prone to ALL while the other three forms of leukemia are more common in adults. Over the last few decades, tremendous development in the treatment of leukemia has taken place with the most recent being the advent of targeted therapy. Various components of the pro-survival signaling pathways have been targeted with the aim to inactivate the signaling and thereby control cancer and prolonging patient survival. Thus, different therapeutic... (More)
Leukemia involves uncontrolled proliferation of different types of blood cells. Accordingly, it is classified as Acute myeloid leukemia (AML), Acute lymphoblastic leukemia (ALL; which includes B cell and T cell – ALL), Chronic myeloid leukemia (CML) and Chronic lymphoblastic leukemia (CLL). Children are more prone to ALL while the other three forms of leukemia are more common in adults. Over the last few decades, tremendous development in the treatment of leukemia has taken place with the most recent being the advent of targeted therapy. Various components of the pro-survival signaling pathways have been targeted with the aim to inactivate the signaling and thereby control cancer and prolonging patient survival. Thus, different therapeutic agents have been used to target various components of the PI3K/AKT/mTOR pathway which is hyperactivated in the majority of cancers such as breast, lung, melanomas, leukemia and so on. Even though many of these drugs have been tested effectively in pre-clinical and clinical settings, they have by and large failed to live up to the expectations of scientists and researchers worldwide. This is mainly due to the relapse that occurs after the treatment as a result of secondary feedback mechanisms. Thus, proper knowledge of the signaling networks and cross-talks between them is required in order to effectively identify and target these pathways.

Mutations in the genes coding for receptor tyrosine kinases (RTKs) and G-protein- coupled receptors (GPCRs) are quite common in all forms of acute leukemia. This can be a major cause of deregulation of PI3K-mTOR pathway. Here, we identified a target gene by screening a panel of acute leukemic cell lines for their sensitivity to the PI3K-mTOR inhibitors. We then generated two groups of cell lines, either sensitive or resistant to the PI3K-mTOR inhibitors and identified a GPCR known as Purinergic receptor 14, P2RY14, as a target gene.

P2RY14 has not been studied well in hematologic malignancies. However, this receptor seems to have important roles in blood cells where it promotes localization of Hematopoietic Stem Cells (HSCs) and prevents their senescence. This receptor also seems to be involved in promoting regenerative capabilities following injury. Nevertheless, further in vitro testing of the receptor functionality with various biochemical and molecular biology techniques is required before this receptor, P2RY14, can be utilized as a therapeutic target in the future treatment of acute leukemia.

Supervisor: Kazi Julhash Uddin
Co-supervisor: Lars Rönnstrand
Master´s Degree Project(60 credits) in Molecular Biology, Molecular Genetics and Biotechnology, 2017
Department of Biology, Lund University (Less)
Please use this url to cite or link to this publication:
author
Shah, Kinjal
supervisor
organization
course
MOBT01 20161
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
8925121
date added to LUP
2017-09-08 16:13:04
date last changed
2017-09-08 16:13:04
@misc{8925121,
  author       = {Shah, Kinjal},
  language     = {eng},
  note         = {Student Paper},
  title        = {Role of the g-protein-coupled receptor p2ry14 in acute leukemia},
  year         = {2017},
}