Association of human leukocyte antigen with precursor-B acute lymphoblastic leukaemia (pre-B ALL) in Malays
Acute Lymphoblastic Leukaemia (ALL) is one of the leukaemia subdivisions and is a malignant disorder of lymphoid progenitor cells originating from the marrow affecting both children and adults. Pathogenesis and epidemiologic studies of leukaemia in some population strongly suggest that this disea...
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| Format: | Thesis |
| Language: | English |
| Published: |
2013
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| Subjects: | |
| Online Access: | http://psasir.upm.edu.my/id/eprint/67671/1/IB%202013%2039%20IR.pdf |
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| Summary: | Acute Lymphoblastic Leukaemia (ALL) is one of the leukaemia subdivisions and is
a malignant disorder of lymphoid progenitor cells originating from the marrow
affecting both children and adults. Pathogenesis and epidemiologic studies of
leukaemia in some population strongly suggest that this disease has an inherited basis
and described an increase in allele frequency of HLA antigens that contribute as one
of the risk factors. Thus, polymorphisms and different HLA genetic make-up in
different ethnic groups make it crucial to study the disease in each population.
Malays make up the largest population in Malaysia and the incidence of lymphoid
leukaemia has also been reported to be highest in this group. It is hypothesised that
there is an increased frequency of certain Class II (HLA-DRB1) alleles and also
increase in levels of soluble HLA-DRB1 in ALL patients. The objectives of this
study were to identify the HLA-DRB1 alleles associated with ALL patients of Malay
ethnicity in Malaysia, and further sequence the identified risk alleles, and determine
the soluble HLA levels in plasma in those patients compared to the healthy
population. HLA-DNA Typing Class II was performed in pre-B ALL patients (n=42)
by PCR-SSO (Polymerase chain reaction, sequence-specific oligonucleotides) and
the data of HLA allele genotypes were compared with available data from healthy
Malay population (n=1445). Furthermore, the plasma levels of soluble HLA class II
(sHLA-DRB1) in patients (n=30) and controls (n=31) were determined by sandwich
Enzyme-linked immunosorbent assay (ELISA). DNA sequencing of specific HLADRB1
alleles for the risk and associated alleles was also carried out on exon 2 by
Sequence based typing (SBT) approach. Results show that there were higher allelic
distribution of specific HLA-DRB1 alleles; HLA-DRB1*03 (P value=0.001,
OR=2.92, 95% CI=1.47-5.80) and also –DRB1*16 (P value=0.001, OR=2.76, 95%
CI=1.30-5.87) observed among Malay pre-B ALL patients. On the other hand,
significant decrease in HLA-DRB1*07 (P value=0.032, OR=0.47, 95% CI=0.17-
1.28) and -DRB1*12 (P value=0.008, OR=0.59, CI=0.33-1.03) were seen in these
patients, would suggest protective potential for the disease. Further analysis by SBT
was able to clarify the resolution of risk alleles, which were HLA-DRB1*03:01:01
and HLA-DRB1*16:02:01, respectively. Polymorphisms were observed between
DNA sequences of polymorphic exon 2 of patient and control groups for –DRB1*03 but not –DRB1*16. An increase in levels of soluble HLA-DRB1 in plasma also was
detected in the ALL patients (0.260 ± 0.057 μg/mL) compared to normal individuals
(0.051 ± 0.007 μg/mL) with p value of 0.001. The results obtained support the earlier
hypothesis and suggest that HLA Class II antigens are the susceptible genes and also
as possible biomarker for ALL. This investigation may contribute to aetiology and
pathogenesis studies on ALL and identify HLA as potential genetic risk markers or
as cancer biomarkers, and also as reference for future studies. |
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