Characteristics of immunologic markers in pediatric acute lymphoblastic leukemia with genetic mutation at national institute of hematology and blood transfusion from 2016 to 2018

T12 Journal of Clinical Medicine - No. 51/2018
 CHARACTERISTICS OF IMMUNOLOGIC MARKERS
 IN PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA WITH GENETIC 
MUTATION AT NATIONAL INSTITUTE OF HEMATOLOGY AND 
BLOOD TRANSFUSION FROM 2016 TO 2018
Hoang Thi Hong1, Mai Lan1, Nguyen Quang Tung1, 
Nguyen Trieu Van1, Bach Quoc Khanh1 
ABSTRACT
diagnosis, treatment and prognosis of pediatric ALL. 
Objective:
National institute of Hematology and Blood transfusion from 2016-2018. 
Methods: Cross-sectional descriptive on 189 pediatric patients aged 1-15 years old with newly 
diagnosis ALL. 
Results. Frequency of fusion genes was 26.9% (fusion gene TEL-AML1 13.2%, BCR-ABL 8.5%, E2A-
PBX1 2.6%, MLL-AF4 2.6%). B - ALL was prevalent with 82.0%; T - ALL accounted for 16.4%. 97,8% of 
the patients with genetic mutation were in group of B-ALL. CD45 showed strong positive expression in 
of CD34 patients was highest in the BCR-ABL1 fusion gene group. The E2A-PBX1 gene mutation group 
was negative for CD34. The presence of CD19, CD79a markers was high in pediatric patients. CD10 (+) 
was low in the MLL-AF4 group. The incidence of CD20 was low in the groups. The incidence of myeloid CD 
was highest in BCR-ABL1 (37.5% positive for CD33), without the presence of myeloid CD in the pediatric 
patients with the E2A- PBX1 and MLL-AF4 fusion gene.
1. National Institute of Hematology 
and Blood transfusion
- Received: 8/8/2018; Revised: 16/8/2018 
- Accepted: 27/8/2018
- Corresponding author: Hoang Thi Hong 
- Email: hoanghong.nihbt@gmail.com. Tel: 0983885350
I. INTRODUCTION
Acute lymphoblastic leukemia (ALL) accounts 
for about 25% of childhood cancers and about 
1% of adult cancers. About 60-70% of ALL 
have genetic changes. The presence of genetic 
alterations and characteristics of immunologic 
markers are important in prognosis, evaluating 
the therapeutic response for ALL [1], [2], [ 3]. 
In Vietnam, the relationship between genetic 
variation and immunological traits has not been 
studied extensively. So we conducted this research 
with the aim:
- Research characteristics of immunologic 
markersin pediatric all with genetic mutation 
in national institute of hematology and blood 
transfusion from 2016 to 2018.
II. SUBJECTS AND METHODS
2.1. Subjects of Study
189 pediatric patients who were diagnosed 
with acute lymphoblastic leukemia newly 
according to the WHO 2008 standard, treated 
Hue Central Hospital
Journal of Clinical Medicine - No. 51/2018 13
in Pediatric Department, National Institute 
of Hematology and Blood Transfusion from 
01/8/2016 to 30/4/2018.
Cross-sectional descriptive 
study
- 
leukemia, aged 1-15. 
No previous chemotherapy or corticosteroids. 
Be fully tested 
The family agrees to participate in the study.
- 
PCR assay for mutation of TEL / AML1, E2A / 
PBX1, BCR / ABL, MLL / AF4 fusion gene.
panel of the NIHBT. 
Analyze characterization of immunologic 
Figure 3.1. Distribution of pediatric patients by sex and age group (n=189)
%
155 82.0
31 16.4
1 0.5
2 1.1
189 100
mixed acute lineage leukemia
14 Journal of Clinical Medicine - No. 51/2018
Research characteristics of immunologic markers...
Table 3.2. Rate of genetic variations in the study (n=189)
%
No gene mutations detected 138 73.1
Fusion genes detected
(n=46, 26.9%)
TEL-AML1 25 13.2
BCR-ABL1 16 8.5
E2A-PBX1 5 2.6
MLL-AF4 5 2.6
189 100
the TEL-AML1 fusion gene accounted for the highest rate of 13.2%. 8.5% of pediatric patients had the 
proportion (2.6%).
 Immune phenotype 
Fusion gene
B-ALL T-ALL Total
TEL-AML1 25 (100%) 0 (0%) 25 (100%)
BCR-ABL1 15 (93,8%) 1 (6,2%) 16 (100%)
E2A-PBX1 5 (100%) 0 (0%) 5 (100%)
MLL-AF4 5 (100%) 0 (0%) 5 (100%)
Total 45 (97,8%) 1 (2,2%) 46 (100%)
(2.2%) had BCR-ABL1 fusion gene in the T-ALL group.
Figure 3.2. Characteristic of CD45 expression in fusion gene groups (n=189)
Hue Central Hospital
Journal of Clinical Medicine - No. 51/2018 15
Table 3.4. Characteristic of CD34 and HLA-DR expression in fusion gene groups (n=189)
 CD
Fusion genes
HLA-DR CD34
Negative Positive Negative Positive
No fusion genes detected 31.2% 68.8% 38.4% 61.6%
TEL-AML1 4.0% 96.0% 24% 76%
BCR-ABL1 18.8% 81.2% 6.2% 93.8%
E2A-PBX1 0% 100% 100% 0%
MLL-AF4 0% 100% 20% 80%
Table 3.5. Characteristic features of B- cell phenotype in fusion gene groups (n=46)
TEL-AML1 BCR-ABL1 E2A-PBX1 MLL-AF4
CD10 (+) 100% 93.8% 100% 20%
CD19 (+) 100% 87.5% 100% 100%
CD20 (+) 12.0% 25.0% 0% 20%
CD79a (+) 100% 93,8% 100% 100%
and did not appear in the E2A-PBX1 fusion gene group.
Table 3.6. Characteristics of abnormalities immune marker in fusion gene groups
TEL-AML1 BCR-ABL1 E2A-PBX1 MLL-AF4
CD13 (+) 4.0% 0 % 0 % 0 %
CD33 (+) 4.0% 37.5% 0% 0%
CD56 (+) 4.0% 6.2% 0% 0%
Our research is similar to that of Mai Lan (2015), 
higher than female, the age group 1-5 represented 
the highest proportion in pediatric ALL patients of 
NIHBT.
.
 The proportion of B-cell ALL patients is 
T-cell ALL patients is 16,4% and the rest is the level 
16 Journal of Clinical Medicine - No. 51/2018
Research characteristics of immunologic markers...
various domestic and international researches. The 
ALL is about 15%. The study of author Hoang Chi 
the percentage of the mixed acute lineage leukemia 
(4,3%). The mixed acute lineage leukemia is rare in 
the genetic expression and got the results that the 
PBX1 2.6%, MLL / AF4 2.6% (Table 3.2).
Table 4.1. Comparing the rate of mutated gene detection with some domestic
 and international studies.
Yanming Zhang-
Michelle M Le Beau
5 25 5 5-7
Terzah M Horton-
C Philip Steuber
3-4 20-25 5 5
Karen Rabin-
3 25 6 8
C.H.Pui 2-3 20-25 4 2
Cheryl L. Willman 2 28 6 4
P.T.D. An 3 25 5 8
10 14 4 2
Our study (n=189) 8.5 13.2 2.6 2.6
Consequently, our proportion of mutated gene 
studies. This may be due to the fact that many 
of Hematology and Blood Transfusion in high risk 
groups, so the frequency of fusion gene detection is 
higher than in other studies.
Table 3.3 illustrates that 97.8% pediatric patients 
B-cell ALL group. Because majority of ALL is B-cell 
the B- cell ALL. Especially, the study encountered 
The literature also reported several instances of 
The research on the characteristics of several 
- In terms of the level of CD45 expression, the 
study found that the CD45-high positive rate (over 
in most groups, especially in the BCR-ABL1 and 
E2A-PBX1 fusion gene group. According to the 
study of author Hoang Chi Cuong, CD45 expres-
-
cytes (95.7%). In our study, the majority of patients 
group, therefore the overall result of strong positive 
the at normal risk population (TEL-AML1) than in 
Hue Central Hospital
Journal of Clinical Medicine - No. 51/2018 17
the high risk g -
-
- Our results present that blast cells in the TEL-
AML1, BCR-ABL1 and MLL-AF4 genetic complex 
HLA-DR and CD34 markers. This result is similar 
(57/57 patients), CD34 positive proportion is 58% 
HLA-DR (+) in all subtypes of B-cell ALL (100%), 
and CD34 positive in 70% of patients [8]. Pediatric 
-
erally positive for CD19, CD10, CD79a, HLA-DR 
but negative for CD34 [10].
- Among the examined hallmarks of B lym-
phocytes, the CD19, CD79a markers had a high 
than other B-type imprints because these mutated 
in less than 6 months of age and older infants, 
-
on there surface [9]. 
- Occurrence of myeloid markers in ALL may be 
observed at rates ranging from 13 to 28% in some 
studies. In our research, the incidence of myeloid 
incidence of myeloid markers is highest in BCR-
cases. Several studies have also found that the inci-
dence of myeloid imprints may be as high as 30% in 
cases of BCR-ABL1 [9].
some conclusions: 
- B-cell ALL accounted for the majority (82%); 
B-cell ALL group.
- A rare case of BCR-ABL1 fusion gene belonged 
to T-cell ALL.
- The CD34-negative count in the E2A-PBX1 
the groups.
ABL1 (37.5% positive for CD33). 
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Research characteristics of immunologic markers...