Study of microenvironment mediated chemoresistance in Chronic Myeloid Leukemia

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Chronic Myeloid Leukemia (CML) is a myelo proliferative disorder in which the leukemic stem cells (LSC) give rise to abnormally high number of myeloid cells. CML is initiated by BCRABL fusion (9;22) (q34;q11) which is the result of reciprocal translocation between chromosome 9 and chromosome 22. BCR-ABL fusion gene codes for Bcr-Abl fusion protein which is a constitutively active tyrosine kinase. Tyrosine kinase inhibitors (TKIs) such as Imatinib mesylate (IM) is the mainline drug used for the treatment of CML. CML responds to IM treatment efficiently, especially in the chronic phase. However, in several patients, CML relapses even after few years of remission, mainly upon discontinuation of IM intake. Mutations in the BCRABL kinase domain have been reported to be the main cause of IM resistance. However, persistent leukemic cells in the BM in spite of IM treatment play a major role in causing relapse in CML patients. BM stromal microenvironment has been implicated to be the major cause of this persistence, where mesenchymal stromal cells (MSC) and their derivatives provide chemoprotection to CML cells through secreted factors as well as direct cell-cell contact.
Supervisor: Bithiah Grace Jaganathan