DELETIONS OF DERIVATIVE CHROMOSOME 9. A MECHANISM OF CLONAL EVOLUTION?

GUTIERREZ L; DE BRASI C; FERRI C; VENTRIGLIA V; FREITAS J; BIANCHINI M; LARRIPA I

Philadelphia

Congreso; 16th Annual John Goldman Conference on Chronic Myeloid Leukemia: Biology and Therapy; 2014

European School of Haematology

Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder characterized, in about 90% of cases, by the reciprocal translocation t(9;22)(q34;q11) that juxtaposes the 3' region of ABL1 to the 5' region of BCR genes. This rearrangement generate a BCR-ABL1 fusion gene on the derivative chromosome 22 (der(22)) known as Philadelphia (Ph) chromosome, and the reciprocal ABL1-BCR on the derivative chromosome 9 (der(9)). The remaining 10% of patients either harbor variant translocations, involving other chromosomes, or cryptic fusions mimicking a normal karyotype. Deletions on der(9) have been reported approximately in 15-30% of CML and can be detected by FISH. These deletions usually involve the ABL1-BCR gene on der(9) and it is believed to take place simultaneously to Ph translocation. The poor prognosis associated with these deletions was postulated to be associated with a mechanism of haploinsufficiency of tumor suppressor genes within the gap. We analyzed a group of 32 CML cases at diagnosis by FISH (dual color-dual fusion) and RT-PCR to analyze BCR-ABL1 and ABL1-BCR transcripts to characterize deletions on der(9). Our results showed that 9/32 (28.1%) had FISH signal patterns consistent with deletions on der(9). In 5/9 cases (54.5%) the absence of the reciprocal ABL1/BCR transcript was confirmed indicating good correlation with FISH results. In the remaining 4/9 (45.5%), it was observed the presence of at least two types of clones by FISH, one showing deletions on der(9) and a second clone without deletions showing both the canonical BCR-ABL1 and the reciprocal ABL1/BCR transcript expressions.