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BACKGROUND: Chronic myelogenous leukemia (CML) results from the neoplastic transformation of a haematopoietic stem cell. The hallmark genetic abnormality of CML is a chimeric BCR/ABL1 fusion gene resulting from the Philadelphia chromosome rearrangement t(9;22)(q34;q11). Clinical and laboratory studies indicate that the BCR/ABL1 fusion protein is essential for initiation, maintenance and progression of CML, yet the event(s) driving the transformation from chronic phase to blast phase are poorly understood. RESULTS: Here we report multiple genome aberrations in a collection of 78 CML and 14 control samples by oligonucleotide array comparative genomic hybridization. We found a unique signature of genome deletions within the immunoglobulin heavy chain (IGH) and T cell receptor regions (TCR), frequently accompanied by concomitant loss of sequences within the short arm regions of chromosomes 7 and 9, including IKZF1, HOXA7, CDKN2A/2B, MLLT3, IFNA/B, RNF38, PAX5, JMJD2C and PDCD1LG2 genes. CONCLUSIONS: None of these genome losses were detected in any of the CML samples with myeloid transformation, chronic phase or controls, indicating that their presence is obligatory for the development of a malignant clone with a lymphoid phenotype. Notably, the coincidental deletions at IGH and TCR regions appear to precede the loss of IKZF1 and/or p16 genes in CML indicating a possible involvement of RAG in these deletions.

Original publication

DOI

10.1186/1471-2164-11-41

Type

Journal article

Journal

BMC genomics

Publication Date

18/01/2010

Volume

11

Addresses

UCL School of Medicine, Cancer Institute, Academic Haematology, Royal Free Campus, Rowland Hill Street, Hampstead, London NW3 2PF, UK. e.nacheva@ucl.ac.uk

Keywords

Chromosomes, Human, Pair 7, Chromosomes, Human, Pair 9, Humans, Blast Crisis, Oligonucleotide Array Sequence Analysis, Computational Biology, Sequence Deletion, Genes, p16, Genes, T-Cell Receptor, Immunoglobulin Heavy Chains, Ikaros Transcription Factor, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Comparative Genomic Hybridization