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

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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.

No MeSH data available.


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.
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Figure 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.

Mentions: FISH screening revealed three patients with more than five RUNX1 signals (Fig. 1). The clinical characteristics of the three patients are summarized in Table 2. MLPA analysis revealed amplification of chromosome 21 in only patient C (Fig. 2). The 32 probes encompassing a 12.5-Mb region around 21q21.3 to 21q22.3, which include NCAM2, BACH1, TIAM1, OLIG2, KCNE2, RUNX1, SIM2, HLCS, DYRK1A, KCNJ6, ERG, ETS2, PSMG1, TMPRSS2, and PIPK4, showed amplification (Fig. 3). The average relative ratio of probes in amplified regions was 2.82 (range, 1.87-3.50), indicating the presence of more than five allele copies compared with the two alleles in normal controls. MIR99A on the proximal site of the amplified region and TFF1, ITGB2, SLC19A1, COL6A2, and PRMT2 on the distal site of the amplified region showed deletion signals. The average relative ratio of probes in the deleted regions was 0.62 (range, 0.53-0.72).


Frequency and Clinical Characteristics of Intrachromosomal Amplification of Chromosome 21 in Korean Childhood B-lineage Acute Lymphoblastic Leukemia
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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940492&req=5

Figure 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.
Mentions: FISH screening revealed three patients with more than five RUNX1 signals (Fig. 1). The clinical characteristics of the three patients are summarized in Table 2. MLPA analysis revealed amplification of chromosome 21 in only patient C (Fig. 2). The 32 probes encompassing a 12.5-Mb region around 21q21.3 to 21q22.3, which include NCAM2, BACH1, TIAM1, OLIG2, KCNE2, RUNX1, SIM2, HLCS, DYRK1A, KCNJ6, ERG, ETS2, PSMG1, TMPRSS2, and PIPK4, showed amplification (Fig. 3). The average relative ratio of probes in amplified regions was 2.82 (range, 1.87-3.50), indicating the presence of more than five allele copies compared with the two alleles in normal controls. MIR99A on the proximal site of the amplified region and TFF1, ITGB2, SLC19A1, COL6A2, and PRMT2 on the distal site of the amplified region showed deletion signals. The average relative ratio of probes in the deleted regions was 0.62 (range, 0.53-0.72).

View Article: PubMed Central - PubMed

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.

No MeSH data available.