Document Detail


Identification of copy number alterations by array comparative genomic hybridization in patients with late chronic or accelerated phase chronic myeloid leukemia treated with imatinib mesylate.
MedLine Citation:
PMID:  21387093     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The outcome of treating chronic myeloid leukemia (CML) with imatinib mesylate (IM) is inferior when therapy is commenced in late chronic or accelerated phase as compared to early chronic phase. This may be attributed to additional genomic alterations that accumulate during disease progression. We sought to identify such lesions in patients showing suboptimal response to IM by performing array-CGH analysis on 39 sequential samples from 15 CML patients. Seventy-four cumulative copy number alterations (CNAs) consisting of 35 losses and 39 gains were identified. Alterations flanking the ABL1 and BCR genes on chromosomes 9 and 22, respectively, were the most common identified lesions with 5 patients losing variable portions of 9q34.11 proximal to ABL1. Losses involving 1p36, 5q31, 17q25, Y and gains of 3q21, 8q24, 22q11, Xp11 were among other recurrent lesions identified. Aberrations were also observed in individual patients, involving regions containing known leukemia-associated genes; CDKN2A/2B, IKZF1, RB1, TLX1, AFF4. CML patients in late stages of their disease, harbor pre-existing and evolving sub-microscopic CNAs that may influence disease progression and IM response.
Authors:
Veera S Nadarajan; Chin-Lee Phan; Chow-Hiang Ang; Kai-Ling Liang; Gin-Gin Gan; Ping-Chong Bee; Zubaidah Zakaria
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-9
Journal Detail:
Title:  International journal of hematology     Volume:  -     ISSN:  1865-3774     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9111627     Medline TA:  Int J Hematol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Pathology, Faculty of Medicine, University Malaya, Lembah Pantai, 50603, Kuala Lumpur, Malaysia, veera@um.edu.my.
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