Characteristics of immunologic markers in pediatric acute lymphoblastic leukemia with genetic mutation at national institute of hematology and blood transfusion from 2016 to 2018
T
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.
I. INTRODUCTION
with the aim:
Acute lymphoblastic leukemia (ALL) accounts
- Research characteristics of immunologic
for about 25% of childhood cancers and about markersin pediatric all with genetic mutation
1% of adult cancers. About 60-70% of ALL in national institute of hematology and blood
have genetic changes. The presence of genetic transfusion from 2016 to 2018.
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
II. SUBJECTS AND METHODS
2.1. Subjects of Study
189 pediatric patients who were diagnosed
variation and immunological traits has not been with acute lymphoblastic leukemia newly
studied extensively. So we conducted this research according to the WHO 2008 standard, treated
1. National Institute of Hematology - Received: 8/8/2018; Revised: 16/8/2018
and Blood transfusion
- Accepted: 27/8/2018
- Corresponding author: Hoang Thi Hong
- Email: hoanghong.nihbt@gmail.com. Tel: 0983885350
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Journal of Clinical Medicine - No. 51/2018
Hue Central Hospital
in Pediatric Department, National Institute
of Hematology and Blood Transfusion from
01/8/2016 to 30/4/2018.
Be fully tested
The family agrees to participate in the study.
-
Cross-sectional descriptive
PCR assay for mutation of TEL / AML1, E2A /
study
-
PBX1, BCR / ABL, MLL / AF4 fusion gene.
panel of the NIHBT.
leukemia, aged 1-15.
Analyze characterization of immunologic
No previous chemotherapy or corticosteroids.
Figure 3.1. Distribution of pediatric patients by sex and age group (n=189)
%
155
31
1
82.0
16.4
0.5
2
1.1
189
100
mixed acute lineage leukemia
Journal of Clinical Medicine - No. 51/2018
13
Research characteristics of immunologic markers...
Table 3.2. Rate of genetic variations in the study (n=189)
%
No gene mutations detected
138
25
16
5
73.1
13.2
8.5
TEL-AML1
BCR-ABL1
E2A-PBX1
MLL-AF4
Fusion genes detected
(n=46, 26.9%)
2.6
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
B-ALL
T-ALL
Total
Fusion gene
TEL-AML1
BCR-ABL1
E2A-PBX1
MLL-AF4
Total
25 (100%)
15 (93,8%)
5 (100%)
0 (0%)
1 (6,2%)
0 (0%)
25 (100%)
16 (100%)
5 (100%)
5 (100%)
46 (100%)
5 (100%)
0 (0%)
45 (97,8%)
1 (2,2%)
(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)
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Journal of Clinical Medicine - No. 51/2018
Hue Central Hospital
Table 3.4. Characteristic of CD34 and HLA-DR expression in fusion gene groups (n=189)
CD HLA-DR CD34
Negative
Fusion genes
Positive
68.8%
96.0%
81.2%
100%
Negative
38.4%
24%
Positive
61.6%
76%
No fusion genes detected
TEL-AML1
31.2%
4.0%
18.8%
0%
BCR-ABL1
6.2%
93.8%
0%
E2A-PBX1
100%
20%
MLL-AF4
0%
100%
80%
Table 3.5. Characteristic features of B- cell phenotype in fusion gene groups (n=46)
TEL-AML1
100%
BCR-ABL1
93.8%
E2A-PBX1
100%
MLL-AF4
20%
CD10 (+)
CD19 (+)
CD20 (+)
CD79a (+)
100%
87.5%
100%
100%
20%
12.0%
25.0%
0%
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
4.0%
BCR-ABL1
0 %
E2A-PBX1
0 %
MLL-AF4
0 %
CD13 (+)
CD33 (+)
CD56 (+)
4.0%
37.5%
6.2%
0%
0%
0%
4.0%
0%
NIHBT.
.
Our research is similar to that of Mai Lan (2015),
The proportion of B-cell ALL patients is
higher than female, the age group 1-5 represented
the highest proportion in pediatric ALL patients of
T-cell ALL patients is 16,4% and the rest is the level
Journal of Clinical Medicine - No. 51/2018
15
Research characteristics of immunologic markers...
(4,3%). The mixed acute lineage leukemia is rare in
various domestic and international researches. The
ALL is about 15%. The study of author Hoang Chi
the genetic expression and got the results that the
PBX1 2.6%, MLL / AF4 2.6% (Table 3.2).
the percentage of the mixed acute lineage leukemia
Table 4.1. Comparing the rate of mutated gene detection with some domestic
and international studies.
Yanming Zhang-
Michelle M Le Beau
5
3-4
3
25
20-25
25
5
5
6
5-7
5
Terzah M Horton-
C Philip Steuber
Karen Rabin-
8
C.H.Pui
2-3
2
20-25
28
4
6
2
4
Cheryl L. Willman
P.T.D. An
3
25
5
8
10
8.5
14
4
2
Our study (n=189)
13.2
2.6
2.6
Consequently, our proportion of mutated gene
The research on the characteristics of several
- In terms of the level of CD45 expression, the
studies. This may be due to the fact that many study found that the CD45-high positive rate (over
of Hematology and Blood Transfusion in high risk in most groups, especially in the BCR-ABL1 and
groups, so the frequency of fusion gene detection is E2A-PBX1 fusion gene group. According to the
higher than in other studies.
study of author Hoang Chi Cuong, CD45 expres-
-
Table 3.3 illustrates that 97.8% pediatric patients cytes (95.7%). In our study, the majority of patients
B-cellALL group. Because majority ofALL is B-cell group, therefore the overall result of strong positive
the B- cell ALL. Especially, the study encountered
The literature also reported several instances of the at normal risk population (TEL-AML1) than in
16
Journal of Clinical Medicine - No. 51/2018
Hue Central Hospital
the high risk g
-
-
- 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
- Our results present that blast cells in the TEL-
AML1, BCR-ABL1 and MLL-AF4 genetic complex
incidence of myeloid markers is highest in BCR-
HLA-DR and CD34 markers. This result is similar
(57/57 patients), CD34 positive proportion is 58%
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].
HLA-DR (+) in all subtypes of B-cell ALL (100%),
and CD34 positive in 70% of patients [8]. Pediatric
some conclusions:
- B-cell ALL accounted for the majority (82%);
-
erally positive for CD19, CD10, CD79a, HLA-DR
but negative for CD34 [10].
B-cell ALL group.
-Arare case of BCR-ABL1 fusion gene belonged
to T-cell ALL.
- Among the examined hallmarks of B lym-
phocytes, the CD19, CD79a markers had a high
than other B-type imprints because these mutated
- The CD34-negative count in the E2A-PBX1
in less than 6 months of age and older infants,
-
the groups.
ABL1 (37.5% positive for CD33).
on there surface [9].
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Blood, 25 june 2015 , volume 125, number 26,
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