Usefulness of Early Diagnosis
The early diagnosis of chronic myeloid leukemia (CML) is extremely important since it is a disease, which if detected early enough in its course, can be cured. The symptomatology of CML is relatively non-specific. Patients present with asthenia, or loss of appetite, sometimes associated with weight loss. Nearly half of the subjects suffering from this disease have no symptoms. The disease is suspected when a blood count shows an increase in leucocytes, with or without an increase in the platelet count, basophilia and often myelemia, i.e. the presence of immature bone marrow cells in the blood. Physical examination will reveal only one sign: splenomegaly (spleen enlargement).
CML is a disease that progresses in three phases: i) a relatively asymptomatic chronic phase; ii) an intermediate accelerated phase where the disease progresses and becomes difficult to treat; and iii) a blastic phase where the disease turns into acute leukemia. Generally speaking, patients in the chronic phase may live several years, but the median duration from onset to death is three years. In the case of the intermediate accelerated or blastic phases, the duration is often only a few months. Hematopoietic stem cell transplants and interferon treatments represent highly beneficial alternatives for these patients. The earlier in the course of the disease that treatment is begun, the better the prognosis, hence the importance of having accurate and sensitive diagnostic tools.

bcr-abl Rearrangement
This molecular abnormality points to a diagnosis of CML. The bcr-abl rearrangement, where bcr stands for "breakpoint cluster region" and abl for "Abelson," results from the aberrant fusion of a part of chromosome 9 with a part of chromosome 22, which generates a small chromosome known as the "Philadelphia chromosome." While the bcr-abl molecular rearrangement is always present in patients with CML, the Philadelphia chromosome may be absent (conventional cytogenetic analysis). In this case, a translocation involving several chromosomes is often involved (masked translocation). Depending on the site of the rearrangement, the fusion gene generates a protein of variable size (185–230 kd). This protein is a kinase protein that activates multiple intracellular signalling pathways and induces exaggerated growth of hematopoietic cells. Moreover, it alters the adhesion of the leukemia cells to the medullar stroma, which probably explains the loss of extrinsic control over proliferation.

Detecting bcr-abl Rearrangement through PCR
The diagnostic test offered by PRO-DNA Diagnostic is performed using PCR (polymerase chain reaction) technology. This highly sensitive and reliable technology makes it possible to detect one rearranged cell among anywhere from 100,000 to one million cells. This is far superior to the accuracy of traditional cytogenetics or of the FISH method (fluorescent in situ hybridation). Moreover, detection of brc-abl rearrangement using PCR technology is fast and low-cost.

Indications for bcr-abl Rearrangement Testing by PCR:

• Inexplicable leucocytosis
  
• Confirmed clinical diagnosis of chronic myeloid leukemia
  
• Other abnormalities in the blood count suggesting a myeloproliferative syndrome, polycythemia, thrombocytosis, myelemia and basophilia
  
• Splenomegaly (enlargement of spleen)
  

Sampling and Characteristics
The genetic test for CML is performed using a blood sample (EDTA tube – 5 ml).
A test report confirming or ruling out the presence of a bcr-abl rearrangement will be sent within less than two weeks.

Terms of Payment
In most cases, private insurance companies will cover the cost of this test.