Artuz, Rex Augustus

Cacao, Juan Carlo

Culvera, Ron
Samson, Rafael

3Bio4
BioSem

Research Topic: Genotyping of Blood Samples collected from Leukemia patients

Adviser: Ms. Catherine Carson
Genotyping is the process of indicating the differences in the genetic make-up of
an individual by examining the individual's DNA sequence using biological assays and
comparing it to another individual's sequence or a reference sequence. In a related
research, the researchers examined the incidence of polymorphic genes involved with
the detoxification of exogenous chemicals, including carcinogens, namely GSTT1
(glutathione transferase theta1), GSTM1 (glutathione transferase micro1) and NQO1
(NAD(P)H:quinone oxidoreductase 1) in 60 Filipino paediatric patients with ALL (acute
lymphoblastic leukaemia). They found out that there is a high incidence of the GSTM1
null and

NQO1 wild-type genotypes among ALL Filipino patients. These findings

suggest a possible role of the GSTM1 null and NQO1 C/C genotypes in the
susceptibility of paediatric ALL cases in the Philippines (Rimando, Chua, Yuson, de
Castro-Bernas and Okamoto, 2008).
Genotyping can also help identify polymorphisms on their respective genes and
by examining them, their effects can be studied. For example, Turkish researchers
identified the polymorphisms on the MDR1 gene and their effects on multidrug
resistance in Acute Leukemia patients. One of the most important proteins, the overexpression of which is responsible for the multidrug resistance phenotype in many
cancer types, is P-glycoprotein. This protein is the product of the MDR1 gene. In
previous studies, single-nucleotide polymorphisms (SNPs) C3435T, G2677T, and T-

129C in the MDR1 gene were shown to be correlated with lower P-glycoprotein
expression in normal tissues. It was suggested that this might have an advantage in
cancer chemotherapy by resulting in a low drug-resistance phenotype (Kaya, Gunduz,
Arpaci, Ural and Guran, 2005).
Genomic polymorphisms can also provide prognostic information in intermediaterisk acute myeloblastic leukemia (Monzo et.al., 2006). Polymorphisms in genes involved
in detoxification and DNA-repair pathways may modify the individual's risk for genomic
damage, and, as a consequence, the risk of developing malignant diseases. The
researchers found a significantly higher prevalence of the polymorphic variants RAD51G135C and CYP3A4-A-290G genes in AML cases, when compared with controls.
Carriers of both the RAD51-G135C and CYP3A4-A-290G variants were at highest AML
risk, suggesting a synergistic effect between these polymorphisms. These results
suggest that polymorphic variants in DNA-repair and detoxification enzymes may cooperate in modulating the individual's risk of AML (Voso et. al., 2007). Also, in another
research, patients with CYP1A1 polymorphism have increased risk of acquiring Acute
Myeloid Leukemia. The research also tackles the detoxifying system which the
carcinogens disrupt thus, leading to DNA damage and development of AML (Pelloso,
Silva, Souza, Yamamoto and Chauffaille, 2013).

References:
Rimando, M., Chua, M., Yuson, E., de Castro-Bernas, G., & Okamoto, T.(2008).
Prevalence of GSTT1, GSTM1 and NQO1 (609C>T) in Filipino children with ALL
(acute lymphoblastic leukaemia). Bioscience Reports, 28(3), 117-124. Retrieved
from http://www.bioscirep.org/bsr/028/0117/bsr0280117.htm

Kaya, P., Gunduz, U., Arpaci, F., Ural, A.U., & Guran, S.(2005). Identification of
Polymorphisms on the MDR1 Gene Among Turkish Population and Their Effects
on Multidrug Resistance in Acute Leukemia Patients. American Journal of
Hematology,
80(1),
26-34.
Retrieved
from
http://onlinelibrary.wiley.com/doi/10.1002/ajh.20427/pdf
Voso M., Fabiani, E., D'Alo', F., Guidi, F., Di Ruscio, A., Sica, S., Pagano, L., Greco,
M., Hohaus, S. & Leone, G. (2007). Increased risk of acute myeloid leukaemia
due to polymorphisms in detoxification and DNA repair enzymes. Annals of
Oncology,
18(9),
1523-1528.
Retrieved
from
http://annonc.oxfordjournals.org/content/18/9/1523.full
Genotyping.
(n.d.).
In
Wikipedia,
Retrieved
http://en.wikipedia.org/wiki/Genotyping

March

2,

2015,

from

Monzo, M., Brunet, S., Urbano-Ispizua, A., Navarro, A., Perea, G., Esteve, J., Artells, R.,
Granell, M., Berlanga, J., Ribera, J., Bueno, J., Llorente, A., Guardia, R., Tormo,
M., Torres, P., Nomdedu, J., Montserrat, E., & Sierra, J. (2006). Genomic
polymorphisms provide prognostic information in intermediate-risk acute
myeloblastic leukemia. Blood Journal, 107(12), 4871-4879. Retrieved from
http://www.bloodjournal.org/content/bloodjournal/107/12/4871.full.pdf
Pelloso, L., Silva, I., Souza, N., Yamamoto M., & Chauffaille, M. (2013). Increased Risk
of Acute Myeloid Leukemia in Patients with CYP1A1 Polymorphisms. Journal of
Cancer Therapy, 4(5), 971-977. doi: 10.4236/jct.2013.45111.
Illmer, T., Schuler, U., Thiede, C., Schwarz, U., Kim, R., Gotthard, S., Freund, D.,
Schkel, U., Ehninger, G., & Schaich, M. (2002). MDR1 Gene Polymorphisms
Affect Therapy Outcome in Acute Myeloid Leukemia Patients. Cancer Research,
62(1),
4955.
Retrieved
from
http://cancerres.aacrjournals.org/content/62/17/4955.full.html
Moon, J., Sohn, S., Lee, M., Jang, J., Kim, K., Jung, C., & Kim, D. (2010). BCL2 gene
polymorphism could predict the treatment outcomes in acute myeloid leukemia
patients. Leukemia Research Journal, 34(2), 166-172. Retrieved from
http://www.lrjournal.com/article/S0145-2126(09)00258-6/abstract
Zhou, W., Zhang, L., Wang, Y., Zhu, B., & Chen, Z. (2012). CYP1A1 MspI polymorphism
and acute myeloid leukemia risk: meta-analyses based on 5018 subjects.
Journal of Experimental and Clinical Cancer Research, 31(1), 62. Retrieved from
http://www.jeccr.com/content/pdf/1756-9966-31-62.pdf
Wu, H., Deng, J., Zheng, J., You, Y., LI, N., Li, W., Wu, D., & Zhou, Y. (2013). Functional
polymorphisms in the CD44 gene and acute myeloid leukemia cancer risk in a
Chinese population. Molecular Carcinogenesis, 54(2), 102-110. Retrieved from
http://onlinelibrary.wiley.com/doi/10.1002/mc.22078/abstract