There are three types of approaches to treating the underlying defect (the BCR-ABL cancer gene – see Explaining CML) in CML.
The initial problem is too many white blood cells (WBCs) in the blood. A high WBC count on a blood test is often how CML is first detected.
So the initial approach is often to reduce the number of WBCs in the blood with a medication such as hydroxyurea (or busulfan, although this is no longer recommended in the European treatment guidelines). Reducing WBCs should result in shrinkage of the spleen and less pain and discomfort in your abdomen. However, these drugs are only a short-term solution because they don’t specifically target the underlying problem in CML.
The second approach is to wipe out the body’s stores of bone marrow (which house the CML defect) and reboot the system. This is accomplished by transplanting stem cells that form blood (called hematopoietic stem cells). The transplant can be obtained from a donor (called an allogeneic transplant, “allos” meaning “other”) or from the person themselves (called autologous, “auto” meaning “self”). Bone a marrow transplantation is the only potential cure for CML. However, to receive marrow transplant, you need a matching donor to avoid tissue rejection. In most types of organ transplantation, the concern is that the body’s immune system will reject the new organ. Bone marrow transplantation is the reverse: since the bone marrow is the source of the immune system, the new transplant may reject the body (i.e. you), which is called graft-versus-host disease (GvHD). This is a serious and sometimes fatal complication of bone marrow transplantation.
The third approach was developed at the turn of the (21st) century with medications that suppress the function of the BCR-ABL gene, thereby shutting off the On signal so that WBCs won’t proliferate unchecked. These medications are called TKIs (for tyrosine kinase inhibitors) and include imatinib (Gleevec), dasatinib (Sprycel), nilotinib (Tasigna) and, in some countries, bosutinib (Bosulif) and ponatinib (Iclusig).
For BCR-ABL to work, it needs to plug into a “battery”. For cells, the energy source is a molecule called ATP (for adenosine triphosphate). This ATP molecule has three phosphates, and one of these is transferred to an amino acid called tyrosine to power it up. The enzyme involved in this transfer is called tyrosine kinase. The tyrosine kinase enzyme is inhibited, as you might expect, by tyrosine kinase inhibitors (TKIs). So in effect, TKIs unplug BCR-ABL from its energy source. On BCR-ABL there is a region (called the kinase domain) and the TKIs insert themselves there much like a key fits into a lock. The TKI key switches off the BCR-ABL signals that are inducing white blood cells to proliferate.