Analysis of Philadelphia chromosome-negative BCR-ABL-positive chronic myelogenous leukemia by hypermetaphase fluorescence in situ hybridization

Background: In 5%-10% of patients with of chronic myelogenous leukemia (CML ), the Philadelphia chromosome (Ph) is not identified, despite the presence of the associated BCR-ABL molecular abnormality (Ph-negative, BCR-ABL-posi tive CML) because of sub-microscopic rearrangements. Patients and methods: Six patients with Ph-negative, BCR-ABL-positive CML w ere investigated. The Ph chromosome detection via fluorescence in situ hybr idization after 24-hour mitotic arrest of bone marrow cultures resulting in several hundreds of metaphases (hypermetaphase FISH or HMF) was useful in explaining the nature of the six cases. Results: Four patients had a low frequency of Ph-positive cells by HMF (5.7 %, 4.8%, 3.9%, 0.2%), i.e., a typical Ph translocation. However, two cases involved a 9q34 inserted into chromosome 22q11 (74.2% and 92%), without a d eletion from chromosome 22 and reciprocal translocation onto 9, i.e., not a typical Ph translocation. The pattern of UBCR gene rearrangement was chara cterized by the same genomic recombination of 5'-BCR and c-ABL, both in the four cases of typical translocation (9;22) and in the two cases of inserti on of 9q34 into chromosome 22q11. Conclusions: The HMF identified two different bases for Ph-negative, BCR-AB L-positive cells in CML - presence of low frequency of cells with typical P h translocations or presence of cells with ABL insertions into the BCR gene on chromosome 22.