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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Viswanatha, D. S. Articles by Willman, C. L. Search for Related Content PubMed PubMed Citation Articles by Viswanatha, D. S. Articles by Willman, C. L. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Characterization and Use of an Antibody Detecting the CBF-SMMHC Fusion Protein in inv(16)/t(16;16)-Associated Acute Myeloid Leukemias David S. Viswanatha, I.-Ming Chen, Pu Paul Liu, Marilyn L. Slovak, Cathy Rankin, David R. Head, and Cheryl L. Willman From the Department of Pathology and Cancer Center, University of New Mexico School of Medicine, Albuquerque, NM; the National Human Genome Research Institute, National Institutes of Health, Bethesda, MD; the City of Hope National Medical Center, Duarte, CA; the Southwest Oncology Group (SWOG) Statistical Center, Seattle, WA; and St Judes Childrens Research Hospital, Memphis, TN. The inv(16)(p13q22) and t(16;16)(p13;q22) cytogenetic abnormalities occur commonly in acute myeloid leukemia (AML), typically associated with French-American-British (FAB) AML-M4Eo subtype. Reverse transcriptase-polymerase chain reaction (RT-PCR) techniques have been recently developed to detect the presence of several variants of the resultant CBFB-MYH11 fusion gene that encodes a CBF-smooth muscle myosin heavy chain (SMMHC) fusion protein. We have now determined the clinical use of a polyclonal antibody [anti-inv(16) Ab] directed against a junctional epitope of the most common type of CBF-SMMHC fusion protein (type A), which is present in 90% of inv(16)/t(16;16) AML cases. Using flow cytometry, reproducible methods were developed for detection of CBF-SMMHC proteins in permeabilized cells; flow cytometric results were then correlated with cytogenetics and RT-PCR detection methods. In an analysis of 42 leukemia cases with various cytogenetic abnormalities and several normal controls, the anti-inv(16) Ab specifically detected all 23 cases that were cytogenetically positive for inv(16) or t(16;16), including a single AML case that was RT-PCR-negative. In addition to detecting all type A fusions, the anti-inv(16) Ab also unexpectedly identified the type C and type D CBF-SMMHC fusion proteins. Molecular characterization of one RT-PCR-positive and Ab-positive t(16;16) case with a non-type A product showed a novel previously unreported CBFB-MYH11 fusion (CBFB nt 455-MYH11 nt 1893). Flow cytometric results were analyzed using the Kolmogorov-Smirnov statistic D-value and the median value for positive samples was 0.65 (range, 0.35 to 0.77) versus 0.07 (range, 0.21 to 0.18) in the negative group (P < .0001). The overall concordance between cytogenetics and RT-PCR was 97%, whereas the concordance between flow cytometry and cytogenetics was 100%. Thus, using the anti-inv(16) Ab, all cytogenetically positive and RT-PCR-positive AML cases with inv(16) or t(16;16) could be rapidly identified. This study demonstrates the use of this antibody as an investigational tool in inv(16)/t(16;16) AML and suggests that the development of such reagents may have potential clinical diagnostic use. Blood, Vol. 91 No. 6 (March 15), 1998: pp. 1882-1890 © 1998 by The American Society of Hematology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. H. Merchant, S. Haines, B. Hall, J. Hozier, and D. S. Viswanatha Fluorescence In Situ Hybridization Identifies Cryptic t(16;16)(p13;q22) Masked By del(16)(q22) in a Case of AML-M4 Eo J. Mol. Diagn., August 1, 2004; 6(3): 271 - 274. [Abstract] [Full Text]

	Copyright © 1998 by American Society of Hematology         Online ISSN: 1528-0020