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Research Journal of Pharmacy and Technology
Year : 2020, Volume : 13, Issue : 6
First page : ( 2971) Last page : ( 2976)
Print ISSN : 0974-3618. Online ISSN : 0974-360X.
Article DOI : 10.5958/0974-360X.2020.00526.0

Review on Pathophysiological and Pharmacotherapeutic approach on Chronic Myeloid Leukemia

Gudimetla Kiranmai1,*, Prabhakar Orsu2, Pal Abhisek1

1GITAM School of Pharmacy, GITAM Deemed to be University, Hyderabad, Telangana

2GITAM Institute of Pharmacy, GITAM Deemed to be University, Visakhapatnam, Andhra Pradesh

*Corresponding Author E-mail: kiranmai.gudimetla@gitam.edu

Online published on 4 July, 2020.

Abstract

Chronic Myeloid Leukemia (CML) is a hematopoietic stem cell malignant clonal disorder resulting in elevation of erythroid cells and platelets in peripheral blood and clear myeloid hyperplasia in the bone marrow. Philadelphia (Ph) chromosome detection forms the major diagnosis in CML. It displays the translocation t(9; 22) that generates the oncogene bcr/abl. Constitutive tyrosine kinase activity is been exhibited by the oncoprotein (BCR/ABL) which supports growth and continued existence in cells of CML. Incidence remains almost constant worldwide and it is the most commonest in India majorly in adults. Clinically, Chronic Phase (CP), Accelerated Phase (AP), and Blast Phase (BP) are the three phases of CML. The drugs used in the treatment of CML are known as Tyrosine Kinase Inhibitors (TKI'S). The primary drug which directly target BCR-ABL tyrosine kinase activity was Imatinib. Imatinib resistance is the major drawback of this drug due to mutations. Imatinib binding is prevented by BCR-ABL kinase domain mutations, BCR-ABL gene amplification or over-expression, clonal progression, and reduced bioavailability of imatinib or cell exposure. Stem cell transplantation is the only curative approach till date. In patients who cannot undergo transplantation, the BCR-ABL tyrosine kinase inhibitor STI571 (Gleevec, Imatinib), immune therapy or interferon-alpha and other cytoprotective drugs are used. Currently available data shows that Imatinib is a better compound compared to second line drugs in producing complete molecular and cytogenetic responses. The resistance against STI571 has been reported which has to be tested with mutational analysis for the treatment for using an accurate regimen. Current researchers are consequently challenging to inhibit or work against STI571 resistance by the development of new molecules or combination of molecules contributing for further improvement in the treatment of CML and for better understanding of resistant mechanisms. These strategies, whether will guide to curative treatment in CML in the future remains unclear.

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Keywords

Chronic Myeloid Leukemia, Tyrosine Kinase Inhibitors, Imatinib, BCR-ABL Onco-protein, Stem Cell Transplantation.

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