Ann Lab Med.  2016 Sep;36(5):475-480. 10.3343/alm.2016.36.5.475.

Frequency and Clinical Characteristics of Intrachromosomal Amplification of Chromosome 21 in Korean Childhood B-lineage Acute Lymphoblastic Leukemia

• Kim J
• Lyu CJ
• Shin S
• Lee ST
• Choi JR

• KMID: 2373579
• DOI: http://doi.org/10.3343/alm.2016.36.5.475

Abstract

BACKGROUND
Intrachromosomal amplification of chromosome 21 (iAMP21) is known to be associated with poor prognosis in B-cell ALL (B-ALL). To determine the frequency and clinical characteristics of iAMP21 in Korean B-ALL patients, we performed FISH and multiplex ligation-dependent probe amplification (MLPA) analyses.
METHODS
A total of 102 childhood B-ALL patients were screened with ETV6-RUNX1 FISH probes (Abbott Molecular, USA). The presence of an iAMP21 was confirmed by using MLPA P327 iAMP21-ERG probemix (MRC Holland, The Netherlands).
RESULTS
iAMP21 was detected in one of the screened B-ALL patients (1/102 patients, 1.0%) who presented the ALL immunophenotype and complex karyotype at initial diagnosis. The patient relapsed twice after bone marrow transplantation. MLPA showed 12.5-Mb and 4.28-Mb regions of amplification and deletion, respectively.
CONCLUSIONS
The frequency of iAMP21 is considerable in Korean pediatric patients. Our report suggests that iAMP21 in childhood B-ALL has very unfavorable impact on patient's prognosis. Additional methods such as MLPA analysis is essential to rule out patients with equivocal interphase FISH results.

Keyword

iAMP21; RUNX1; ERG; FISH; MLPA; Acute lymphoblastic leukemia; Korean; Childhood

MeSH Terms

Adolescent
Asian Continental Ancestry Group/*genetics
B-Lymphocytes/*metabolism
Child
Child, Preschool
*Chromosomes, Human, Pair 21
Core Binding Factor Alpha 2 Subunit/genetics
DNA Probes/metabolism
Female
Humans
Immunophenotyping
In Situ Hybridization, Fluorescence
Infant
Infant, Newborn
Male
Multiplex Polymerase Chain Reaction
Precursor Cell Lymphoblastic Leukemia-Lymphoma/*diagnosis/genetics
Proto-Oncogene Proteins c-ets/genetics
Repressor Proteins/genetics
Republic of Korea
Translocation, Genetic
Young Adult
Core Binding Factor Alpha 2 Subunit
DNA Probes
Proto-Oncogene Proteins c-ets
Repressor Proteins

Figure

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  Fig. 1 FISH analysis using ETV6-RUNX1 dual fusion probe revealed increments of the RUNX1 signal in three patients (A, B, and C). The RUNX1 signals are indicated in orange, and the ETV6 signals are indicated in green.

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  Fig. 2 Multiplex ligation-dependent probe amplification analysis of three patients (A, B, and C). The control peaks are indicated in red, and the patients' peaks are indicated in blue; amplification of multiple probe sites on 21q21.1-21q22.3 was observed in patient C.

• 

  Fig. 3 Schematic representation of regions of amplification and deletion on chromosome 21. The x-axis in the graph indicates the genomic position of the multiplex ligation-dependent probe amplification (MLPA) probe site mapped to the human reference genome hg19. The y-axis indicates ratios of the patients' fluorescence peak height relative to the controls' peak height, as determined by MLPA analysis. Regions of amplification are highlighted in red and regions of deletion are highlighted in blue.

• 

  Fig. 4 Clinical course of patient C. The x-axis in the graph indicates the time (months) after diagnosis. The y-axis indicates the percent of blast count in bone marrow (blue line) and percent recipient chimerism as measured by short tandem repeat analysis (red line). RUNX1 signal amplification by FISH analysis was detected at 13 days after diagnosis, first relapse, and second relapse.

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