Abstract

IBRUTINIB THERAPY FOR LYMPHOCYTIC LEUKEMIA AND RESISTANCE MECHANISM FOR BRUTON’S TYROSINE KINASE INHIBITOR: A REVIEW

*Riya Johns and Dr. Steffi John

.

Abstract

Chronic lymphocytic leukemia (CLL) is a cancer of the blood and, bone marrow that usually gets worse slowly. The treatment options depend on the red blood cell, white blood cells and platelet blood counts, whether the spleen, liver or lymph nodes are larger than normal, the age and, health of the patient at the time of diagnosis, whether there are signs or, symptoms, such as fever, chills, or, weight loss, the response to initial treatment and whether the CLL has recurred. Tyrosine kinase inhibitor therapy blocks the enzyme, tyrosine kinase, that causes stem cells to develop into more white blood cells than the body needs. TKI’s target the abnormal BCR- ABL1 protein that causes uncontrolled CML cell growth and, blocks its function, causing the CML cells to die. Ibrutinib is an orally bioavailable, irreversible selective Bruton’s tyrosine kinase inhibitor that has demonstrated impressive therapeutic effects in patients with B cell malignancies. BTK inhibitor treatment of CLL is limited by either primary or, secondary, i.e., acquired drug resistance. Despite the promising activity of ibrutinib across multiple B-cell lymphoma subtypes, almost one third of patients have primary intrinsic resistance, while many others appear to develop acquired resistance. Resistance to noncovalent BTK inhibitors arose through on target BTK mutations and, downstream PLCγ2 mutations that allowed escape from BTK inhibition. New mechanism of genomic escape from established covalent and, novel noncovalent BTK inhibitors. This review is focused on the resistance of Ibrutinib, a BTK inhibitor and, its resistance mechanism by reviewing literatures from the past 10 years.

Keywords: Chronic lymphocytic leukemia, Bruton’s Tyrosine kinase inhibitors, Ibrutinib, Drug resistance, Acquired resistance.