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Deletions of Immunoglobulin heavy chain and T cell receptor gene regions are uniquely associated with lymphoid blast transformation of chronic myeloid leukemia

Elisabeth P Nacheva1*, Diana Brazma1, Anna Virgili1, Julie Howard-Reeves1, Anastasios Chanalaris1, Katya Gancheva2, Margarita Apostolova2, Mikel Valgañon1, Helen Mazzullo1 and Colin Grace1

Author Affiliations

1 UCL School of Medicine, Cancer Institute, Academic Haematology, Royal Free Campus, Rowland Hill Street, Hampstead, London, NW3 2PF, UK

2 Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia, Bulgaria

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BMC Genomics 2010, 11:41  doi:10.1186/1471-2164-11-41

Published: 18 January 2010



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.


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.


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.