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What is CML?
Ph+ CML (chronic myeloid leukaemia) is a leukaemia that grows slowly eventually produces too many immature white blood cells to form in the bone marrow. Normal blood cells grow and divide to form new blood cells as the body needs them. When blood cells grow old, or are damaged, they normally die through a natural mechanism called apoptosis. Ph+ CML cells evade this mechanism and instead continue to make new (daughter) cells that eventually over populate the marrow and crowd out the normal white cell population.
How does CML develop?
The Philadelphia chromosome is an acquired genetic abnormality and is the definitive marker for Ph+ CML. CML is not an inherited disease and cannot be passed on to children.
The mechanism is known as a reciprocal translocation when a piece from the lower region of chromosome 9 which contains the ABL1 gene, breaks off and attaches to the region on chromosome 22 where the BCR gene is located. These genes then fuse to form a new (abnormal) chromosome 22 containing the (abnormal) fusion gene called BCR-ABL1. It is not definitively understood why this happens. The new chromosome 22 with its fusion gene Bcr/Abl is called the Philadelphia chromosome.
CML has three phases
The first or chronic stage (CP) of CML is characterised by a marked increase in the numbers of normal-appearing white blood cells and sometimes platelets. During the course of the disease, more and more abnormal white cells populate the bone marrow and eventually spill over into the peripheral blood.
Without effective treatment, these abnormal cells undergo even more changes and the disease progresses to accelerated phase (AP) and then inevitably to the end stage of the disease called the blast phase. In blast phase only very immature white cells (blast cells) populate the marrow and blood. In this phase the disease behaves more like an acute leukaemia and is very difficult to treat effectively.
- Chronic phase: An initial period that may last some years during which the disease progresses very slowly. Most people are diagnosed in this phase.
- Accelerated phase: The disease begins to progress more quickly and symptoms often be more problematic. TKI therapies can be less effective for some patients although a significant percentage do response very well to 2nd and 3rd generation TKIs.
- Blast phase: Immature white cells (blasts) become prevalent and the symptoms becomes much worse. This phase behave more like an acute leukaemia and can last up to 3 months. Patients in blast phase will need more intensive medical interventions such as high dose chemotherapy and, in physically eligible patients with a well matched donor, a Stem Cell Transplant.
Who gets Chronic Myeloid Leukaemia?
Ph+ Chronic myeloid leukaemia (Ph+ CML) is a rare disease (1.5 in 100,000 per population) most often develops in adults between the ages of 40 to 65. It is rare in young adults under 19 years and ultra rare in children and babies.