Genomic profile of chronic myelogenous leukemia: Imbalances associated with disease progression

Brazma, D., Grace, C., Howard, J., Melo, J., Holyoake, T., Apperley, J. and Nacheva, E. (2007) Genomic profile of chronic myelogenous leukemia: Imbalances associated with disease progression. Genes, Chromosomes and Cancer, 46(11), pp. 1039-1050. (doi: 10.1002/gcc.20487)

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Abstract

The expression of the chimeric BCR/ABL1 fusion gene resulting from t(9;22)(q34;q11) in chronic myelogenous leukemia (CML) is necessary for malignant transformation, but not sufficient to maintain disease progression. The appearance of various chromosomal and molecular alterations in the accelerated and terminal phase of CML is well documented, but evidence for causal relationship is largely lacking. We carried out a genome wide screening at a resolution of 1 Mb of 54 samples at different stages of CML together with 12 CML cell lines and found that disease progression is accompanied by a spectrum of recurrent genome imbalances. Among the most frequent are losses at Ip36, Sq21, 9p21, and 9q34 and gains at 1q, 8q24, 9q34, 16p, and 22q11, all of which were located with higher precision within the genome than previously possible. These genome imbalances are unique to CIVIL cases with clinically manifested or suspected accelerated/blast stage alike, but not seen in chronic phase samples. Previously unrecognized cryptic imbalances occurring within the Ph-chromosome were also detected, although further scrutiny is required to pin-point gene involvement and seek association with disease features. Importantly, some of these imbalances were seen in the CD34(+) cells but not in the whole BM samples of patients in accelerated phase. Taken together, these findings highlight the potential of screening CD34(+) cells for genome wide imbalances associated with disease progression. Finally, the numerous single copy number variations recorded, many unique to this cohort of patients, raise the possible association of genome polymorphism and CML

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Holyoake, Professor Tessa
Authors: Brazma, D., Grace, C., Howard, J., Melo, J., Holyoake, T., Apperley, J., and Nacheva, E.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Genes, Chromosomes and Cancer
Publisher:Wiley
ISSN:1045-2257

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