Blood Res.  2017 Jun;52(2):100-105. 10.5045/br.2017.52.2.100.

Intrachromosomal amplification of chromosome 21 in Korean pediatric patients with B-cell precursor acute lymphoblastic leukemia in a single institution

• Yang M
• Yi ES
• Kim HJ
• Yoo KH
• Koo HH
• Kim SH

• KMID: 2413326
• DOI: http://doi.org/10.5045/br.2017.52.2.100

Abstract

BACKGROUND
Intrachromosomal amplification of chromosome 21 (iAMP21), defined as the presence of three or more RUNX1 signals on one marker chromosome, is a distinct cytogenetic subgroup of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) that is known to have a poor prognosis when treated with standard therapy. The aim of this study was to evaluate the clinical characteristics of Korean children with iAMP21.
METHODS
The cytogenetic data from BCP-ALL children were reviewed. The ETV6/RUNX1 ES Dual Color Probe was used for fluorescence in situ hybridization (FISH).
RESULTS
In total, 295 children were included. Of these, 10 patients (3.4%) had iAMP21. The median age of iAMP21 patients was 9 years, and the median value of white blood cell count was 5.09×10⁹/L. Slow early treatment response was observed more in iAMP21 patients. Patients with iAMP21 had a higher incidence of relapse and worse survival rates. In patients with iAMP21, the estimated 10-year cumulative incidence of relapse was 53.3%. The estimated 10-year event-free survival and overall survival rate were 46.7% and 64.8%, respectively. Most cases of leukemic relapse developed in the late period (median, 43 mo). In multivariate analysis, high risk group was the only factor that had a significant impact on death.
CONCLUSION
The existence of iAMP21 was related to delayed treatment response and was likely to affect increased relapse and death in the late period. Further studies are needed to reveal its effect on BCP-ALL treatment outcomes and its role as an independent prognostic factor.

Keyword

iAMP21; Childhood BCP-ALL; FISH

MeSH Terms

B-Lymphocytes*
Child
Chromosomes, Human, Pair 21*
Cytogenetics
Disease-Free Survival
Fluorescence
Humans
In Situ Hybridization
Incidence
Leukocyte Count
Multivariate Analysis
Precursor Cell Lymphoblastic Leukemia-Lymphoma*
Prognosis
Recurrence
Survival Rate

Figure

• 

  Fig. 1 LSI ETV6/RUNX1 ES Dual Color Probe revealed increased signals of RUNX1 (red). (A) An interphase cell and metaphase cell from case 6. The cluster of red signals indicates amplification of RUNX1 on the abnormal chromosome 21. (B) An interphase cell from case 10. (C) Metaphase FISH analysis from case 10 confirms that the clustered red signals are on one chromosome (arrow).

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  Fig. 2 The cumulative incidence of relapse by iAMP21. There was a trend toward a higher cumulative incidence of relapse in the iAMP21 group without statistical significance (P=0.102).

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  Fig. 3 (A) The event-free survival (EFS) and (B) overall survival (OS). Patients with iAMP21 were likely to have worse survival rates although there was no statistical significance. The intersection of survival curve of each group was observed at around 5 years after diagnosis in EFS and OS.

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