Chronic Myeloid Leukemia (CML) involves abnormal blood cells that fundamentally alter the body’s normal processes. Understanding these cells is central to comprehending this cancer, including how it develops, progresses, and is managed.
What Are CML Cells?
CML cells are abnormal myeloid cells that originate within the bone marrow, the soft, spongy tissue inside bones where blood cells are produced. In CML, the bone marrow produces an excessive number of these myeloid cells, also known as granulocytes, which then accumulate in the bloodstream.
These abnormal cells interfere with the production of healthy blood cells by crowding the bone marrow. They do not mature properly and are unable to function effectively in fighting infections. This overproduction and accumulation of immature cells can lead to various complications, as they displace normal blood components.
The Genetic Change in CML Cells
The defining genetic alteration in CML cells is the presence of the Philadelphia chromosome. This abnormal chromosome 22 arises from a specific type of genetic rearrangement called a reciprocal translocation. During this process, a segment of chromosome 9 breaks off and exchanges places with a segment of chromosome 22.
This exchange results in a shortened chromosome 22 and creates a new fusion gene called BCR-ABL. The BCR-ABL gene then produces an abnormal protein, also referred to as BCR-ABL protein or p210 BCR-ABL, which has constantly active tyrosine kinase activity. This constant activity of the BCR-ABL protein drives the uncontrolled growth and survival characteristic of CML cells. This genetic change is acquired after birth and is not inherited.
How CML Cells Behave Differently
The presence of the BCR-ABL protein fundamentally alters the behavior of CML cells compared to healthy blood cells. One significant change is uncontrolled proliferation, meaning these cells divide excessively and continuously. Unlike normal cells, CML cells do not mature properly, contributing to their accumulation.
CML cells also exhibit reduced programmed cell death (apoptosis). The BCR-ABL protein actively inhibits this process, allowing the abnormal cells to resist dying. This resistance to programmed cell death, combined with their excessive division, leads to a significant build-up of these abnormal cells. This accumulation occurs primarily in the bone marrow and blood, and can sometimes extend to other organs, disrupting normal bodily functions.
Targeting CML Cells in Treatment
The unique characteristics of CML cells, particularly the constant activity of the BCR-ABL protein, have transformed the approach to CML treatment. Modern therapies for CML are based on the concept of “targeted therapy,” which specifically aims to block the activity of this abnormal protein. Tyrosine kinase inhibitors (TKIs) are a class of drugs designed to achieve this.
TKIs work by attaching to the BCR-ABL protein and preventing it from functioning, thereby inhibiting the uncontrolled growth and survival of CML cells. This targeted approach is highly effective because it directly addresses the underlying cause of the disease, largely sparing healthy cells from damage, unlike traditional chemotherapy. This precise mechanism of action has led to dramatically improved long-term survival rates and revolutionized the management of CML. Patients typically take these medications indefinitely to maintain disease control.