ABSTRACT

Chronic myeloid leukemia which is also known as chronic myelogenous leukemia, is a slow growing cancer of blood forming tissue. A genetic change leads to abnormal behaviour of blood producing myeloid cells, turning out uncontrolled growth of these cells. The primary reason is translocation of t(9,22), where parts of ABL1 gene from chromosome 9 fuses with BCR gene from chromosome 22, leading to form abnormal fusion gene named as BCR-ABL1. Depending upon the stages of disease, different therapies are chosen to treat the patient. Currently most used and successful therapies is Targeted tumour suppressor therapies which are inhibitors of tyrosine kinase, where drugs are targeted against BCL-ABL1 Tyrosine kinase, leading to downregulation and blockage of transformed leukemia cells. However, every treatment comes with its limitation. Even though TKI targeted therapy has increase life expectancy of CML patients, there is notable resistance against these drugs with gradual time increase. Thus, limitation with primary and secondary treatments using these drugs has opened doors to more advanced research to overcome this. In my opinion, current targeted therapy for CML is effective but this needs improvement in regard to increase efficacy, to overcome resistance and to lower down adverse drug effects. The development of more proof-reading technology is needed to cure this condition and for this to effect, more in depth molecular probes are needed in area of CML and followed by one or more therapies may be combined to control the progression of disease, thus increasing life expectancy of CML patients.

Keywords: Tumour suppressor, TKI (Tyrosine kinase inhibitors), BCL-ABR1, chronic myeloid leukemia, Imatinib, AlloSCT, Apoptosis

INTRODUCTION

The current opinion paper is based on one of the cancer forms which arise from bone marrow and its targeted therapies along with its advantage and drawbacks, mentioning the future prospective to inhibit progression of disease. Chronic myeloid leukemia (CML) is one of the life-threatening cancers of bone marrow, which is blood forming tissue. This starts with stem cells present in blood, giving rise to uncontrolled growth of blast cells leading to over production of abnormal cells. The central reason of this pathogenesis is the fusion of Abelson murine leukemia (ABL1) gene on chromosome 9 with cluster region (BCR) gene on chromosome 22. This fusion leads to express oncoprotein called as BCR-ABL1. This is constitutively activated tyrosine kinase, leading to promotion of growth and activation of downstream pathways involving RAS, MYC, STAT. This results in cytokine independent cell cycle with interfered apoptotic signals in response to cytokine withdrawals (Konopleva 2017). The mechanism has been introduced in
figure 1.