Molecular Biology for BCR-ABL1 Quantification for Chronic Myeloid Leukemia Monitorization and Evaluation

Abstract

Chronic Myeloid Leukemia (CML) is a clonal disorder originated by a pluripotent hematopoietic stem cell, which presents the translocation t(9;22) (q34;q11) in 90% of the cases. This genetic abnormality is a balanced translocation between Abelson Murine Leukemia (ABL) located in chromosome 9 with the Breakpoint Cluster Region (BCR) gene at chromosome 22, generating Philadelphia chromosome (Ph) or BCR-ABL1, which codes an oncoprotein of 210 kDa [1-4]. This alteration represents a hallmark in oncology and for CML research, diagnosis, and prognosis. The standard treatment of CML patients is with Tyrosine Kinase Inhibitors (TKIs), and the first line is Imatinib [5]. This drug was developed in 1990s by Brian Druker and Nicholas Lydon and in 1998 a phase 1 clinical trial was conducted, causing cancer regression in most patients with CML in chronic phase. Five years later, 98% of patients from this trial were still in remission. In 2001, this drug was approved by FDA, revolutionizing the treatment of CML. Imatinib is quite selective for BCRABL1 onco-protein, so it does not inhibit other tyrosine kinase enzymes, so far representing one of the pioneers in oncological targeted therapy [6].