CML (chronic myelogenous leukemia) is a blood cell cancer that starts in an hematopoietic stem cell inside bone marrow, as a result of the t(9;22)(q34;q11) reciprocal chromosomal translocation. Simultaneous breaks in the BCR gene on chromosome 22 and the ABL gene on chromosome 9 and the subsequent recombination give rise to an extra-short chromosome 22 (also called the Philadelphia chromosome) and an extra-long chromosome 9. The fusion oncogene created on the Philadelphia chromosome is called BCR-ABL, which encodes for a constitutively active tyrosine kinase BCR-ABL. BCR-ABL-positive cells have faster growth and proliferation rate compared to their normal counterparts. The result is an uncontrolled growth of immature myeloid cells (a certain type of white blood cell) built up in both bone marrow and blood.
CML is a chronic disease, meaning that it develops slowly over time. It is mostly seen in older adults and it is much rarer in children. Some symptoms include easy bleeding, feeling tired, fever, frequent weight loss, pain in the left side of ribs, and sweating excessively at night. One is most likely to be diagnosed with this disease if they are of an older age, male, and had been exposed to radiation. This is not a hereditary disease, as it develops after birth. The mechanism that leads to t(9;22) translocation is unclear. Radiation has been suggested a possible cause, because of the high incidence of CML in Japan following the atomic bombing of Hiroshima and Nagasaki.
CML can be treated with a tyrosine kinase inhibitor, such as Imatinib, which inhibits the BCR-ABL by competitive binding at the ATP-binding site. However, the only known cure for CML is a bone marrow transplant, or stem cell transplant, in which doctors will use high doses of chemotherapy drugs to kill all blood-forming cells, then transfer bone marrow stem cells from healthy donors.