Cytogenetic Profile of Variant Philadelphia Translocations in Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterised by the presence of the Philadelphia (Ph) chromosome which is due to the reciprocal translocation, t(9;22)(q34;q11.2). The translocation results in the BCR-ABL1 fusion gene, encoding a constitutively active tyrosine kinase protein which causes the genesis of CML. About 5-10% of newly diagnosed Ph-positive CML patients have a variant translocation involving chromosomes 9 and 22, and one or more than one other chromosomes. The objectives of this study are to identify the chromosomes involved, breakpoints and additional chromosomal aberrations in variant Ph translocation. Conventional cytogenetic analysis is performed as a routine diagnostic test for all patients with hematological malignancies in our Cytogenetic Laboratory. Based on cytogenetic findings, 42 newly diagnosed CML patients with variant Ph translocation were selected for this study. Thirty nine patients (93%) had simple variant translocation and three patients (7%), complex variant translocation. Besides chromosomes 9 and 22, a total of 16 different chromosomes were involved in variant Ph translocation. The most frequently involved chromosomes were chromosomes 1 and 11. A total of 34 breakpoints were identified. Additional chromosomal abnormalities such as trisomies, translocations, and deletions were also observed. This shows that variant Ph translocations are very heterogeneous at the genetics level, with the involvement of different chromosomes and a diversity of breakpoints.