Korean J Lab Med.  2009 Oct;29(5):371-378. 10.3343/kjlm.2009.29.5.371.

Clinical Utility of Fluorescence in-situ Hybridization Profile Test in Detecting Genetic Aberrations in Acute Leukemia

• Kim SR
• Kim HJ
• Kim SH

• KMID: 1077410
• DOI: http://doi.org/10.3343/kjlm.2009.29.5.371

Abstract

BACKGROUND
Cytogenetic abnormalities are one of the most reliable prognostic factors in acute leukemia. Combination of conventional chromosome analysis (CCA) and FISH provides higher sensitivity in detecting these genetic abnormalities, and it is effective to apply several FISH probes as a profile test. The objective of this study was to investigate the utility of FISH profile analyses in the initial diagnosis of acute leukemia.
METHODS
Two hundred and forty one de novo acute leukemia patients diagnosed from January, 2002 to November, 2007 were included. For acute lymphoblastic leukemia profile test, FISH probes for BCR/ABL, TEL/AML1, MLL gene rearrangement and CDKN2A deletion were used. For acute myeloid leukemia profile test, probes for AML1/ETO, MLL and CBFbeta gene rearrangement were used. The results of CCA and FISH profile tests were collected, and the positive rates were compared.
RESULTS
ALL FISH profile tests revealed additional genetic aberrations not detected by chromosome analysis in 48.6% (67/138) of cases, including those with normal karyotypes or no mitotic cells (37%, 51/138). Among these 51 cases, TEL/AML1 abnormalities were detected in 44.3%, followed by the abnormal CDKN2A signal (24.6%) and hyperdiploidy (18.0%). AML FISH profile tests revealed additional genetic abnormalities in 7.8% (8/103) of cases.
CONCLUSIONS
FISH analysis as a profile test detected additional genetic aberrations in a significant proportion of acute leukemia, and was effective especially in detecting cryptic translocations, submicroscopic deletions and complex karyotypes. Our study supports the need to incorporate FISH profile test at initial work up in acute leukemia.

Keyword

Acute leukemia; Cytogenetic analysis; Fluorescence in-situ hybridization

MeSH Terms

Adolescent
Adult
Child
Child, Preschool
*Chromosome Aberrations
Core Binding Factor Alpha 2 Subunit/genetics
Core Binding Factor beta Subunit/genetics
Cyclin-Dependent Kinase Inhibitor p16/genetics
Female
Humans
In Situ Hybridization, Fluorescence/*methods
Infant
Infant, Newborn
Karyotyping
Leukemia, Myeloid, Acute/*diagnosis/genetics
Male
Middle Aged
Myeloid-Lymphoid Leukemia Protein/genetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma/*diagnosis/genetics
Proto-Oncogene Proteins c-bcr/genetics

Figure

• 

  Fig. 1. Karyotype by conventional chromosome analysis (A) and the FISH patterns showing CBFβ break-apart signals (B) shown in case 1.

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