9;22 – BCR/ABL

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ABL-BCR translocation, t(9;22)

The t(9;22)(q34;q11.2) translocation fuses ABL proto-oncogene on chromosome 9 with the BCR (breakpoint cluster region) region located on chromosome 22, leading to the formation of the Philadelphia chromosome (Ph) and the formation of two hybrid genes. The first gene is BCR-ABL (major), located on the long arm of chromosome 22 or chromosome Ph, produces a constitutively active tyrosine kinase that promotes cell survival and continued proliferation and inhibits apoptosis. This chimeric protein is sensitive to tyrosine kinase inhibitors (imatinib). The resulting second gene, BCR-ABL (minor) is located on chromosome 9q+, is reciprocal to the first gene and does not appear to play any role in the disease. The rapid identification of this chromosomal abnormality is vital, because in a few cases the translocation is not demonstrated by conventional cytogenetics, so the FISH study is essential to reveal the fused gene.

In ALL, the breakpoint in the BCR gene can be in M-bcr or in the minor centromeric region (m-bcr). Chromosomal translocation t(9;22)(q34;q11) is also observed in rare cases of AML. In CML, the breakpoint in BCR is usually in the major (M-bcr) region and the BCR/ABL fusion occurs in virtually all cases of CML. The most common is Philadelphia chromosome t(9;22), but 5-10% of cases of CML show cryptic translocations or variants, which are more difficult to detect by conventional karyotype. Other myeloproliferative disorders not showing t(9:22) or (Ph-) are usually related to somatic mutations in other genes.

Patients with t(9;22)(q34;q11) are characterized by resistance to chemotherapy and poor prognosis. Several studies indicate that treatment with imatinib (Gleevec) eliminates this prognostic factor, while other studies suggest that in patients treated with imatinib, the time of disease progression is significantly shorter.

References

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