Diagnosis and Treatment: Leukemia, chronic myeloid

Chronic myeloid leukemia (CML) is a cancer of blood cells, characterized by replacement of the bone marrow with malignant, leukemic cells. Many of these leukemic cells can be found circulating in the blood and can cause enlargement of the spleen, liver, and other organs. CML is usually diagnosed by finding a specific chromosomal abnormality called the Philadelphia (Ph) chromosome (see figure), named after the city where it was first recorded. The Ph chromosome is the result of a translocation-or exchange of genetic material-between the long arms of chromosomes 9 and 22 . This exchange brings together two genes: the BCR (breakpoint cluster region) gene on chromosome 22 and the proto-oncogene ABL (Ableson leukemia virus) on chromosome 9. The resulting hybrid gene BCR-ABL codes for a fusion protein with tyrosine kinase activity, which activates signal transduction pathways, leading to uncontrolled cell growth. A mouse model has been created that develops a CML-like disease when given bone marrow cells infected with a virus containing the BCR-ABL gene. In other animal models, the fusion proteins have been shown to transform normal blood precursor cells to malignant cells. To research the human disease, antisense oligomers (short DNA segments) that block BCR-ABL were developed that specifically suppressed the formation of leukemic cells while not affecting the normal bone marrow cell development. These and other experimental techniques may lead to future treatments for CML.

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Important Links
Gene sequence
LocusLink [www.ncbi.nlm.nih.gov/LocusLink/list.cgi?Q=BCR%20OR%20ABLa&ORG=Hs&V=0] collection of gene-related
information
BLink [www.ncbi.nlm.nih.gov/sutils/blink.cgi?pid=11038639&org=1]