Integration of amplified BCR/ABL fusion genes into the short arm of chromosome 17 as a novel mechanism of disease progression in chronic myeloid leukemia

Abstract

We describe the cases of two patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML), in whom the extramedullary blastic phase developed during disease progression. The similar clinical presentations of these patients was accompanied by gain of identical secondary chromosome abnormalities, that is, monosomies 9, 14, and 22, and by a clustered amplification of the BCR/ABL fusion gene. The additional copies of the BCR/ABL fusion gene were integrated into the short arm of structurally abnormal chromosomes 17 in both patients. The conformity of these genetic features in two patients with a rare disease manifestation leads us to the assumption that either the clustered amplification of the BCR/ABL fusion gene or the integration of this cluster into the short arm of chromosome 17 or both are associated with extramedullar disease progression in CML. Furthermore, the insertion of amplified BCR/ABL fusion genes into structurally abnormal chromosomes provides a novel mechanism of disease progression in BCR/ABL-positive CML.

Marrow fibrosis predicts early fatal marrow failure in patients with myelodysplastic syndromes

“…Fluorescence R-banding analysis was performed by staining with chromomycin A3 and counterstaining with methyl green as described earlier. 24 Cytogenetic findings were described according to ISCN 1995, 25 and among the patients with an MDS, the cytogenetic risk groups were defined as described by the International Prognostic Scoring Group. 20 JAK-2 V617F mutation.…”

Unusual case of leukemic mantle cell lymphoma with amplified CCND1/IGH fusion gene

“…Actual mechanisms involved in this process include extra replication, unequal sisterchromatid exchange, double-stranded breaks at fragile sites, and erroneous repair (Schwab, 1999). Recently, a similar abnormality was described in primary tumor material from two cases of chronic myelogenous leukemia with clusters of BCR/ABL fusion gene amplified and inserted into chromosome 17 (Metzke-Heidemann et al, 2001). Other fusion gene amplifications are described in solid tumors, e.g., the PAX7/FKHR fusion gene, arising as a result of chromosomal translocation t(1; 13)(p36;q14) or more rarely amplification of PAX3/ FKHR associated with most alveolar rhabdomyosarcomas (Barr et al, 1996;Weber-Hall et al, 1996).…”

High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics

“…13,14 Conventional cytogenetic studies were performed using standard techniques, and chromosomal abnormalities were described according to the International System for Human Cytogenetic Nomenclature. 15 All specimens were also analyzed by FISH using a comprehensive DNA probe set allowing for the detection of the most relevant AML-associated genomic aberrations.…”