Genetic Polymorphism of the Acute Lymphoblastic Leukaemia and Hyperhomocysteinemia its Relation with the for a Group of Children in the East of Algeria
A lot of recent research have spoken on the relation
between the increase of the homocysteinemia and some kinds of
cancer . For that, our study was based on the research of a possible
relation between the increase of the concentration of this amino-acid
in the plasma and the appearance of the disease of the Acute
Lymphoblastic Leukaemia in a part of Algerian children with Berber
origin in the East of Algeria . The study has done on 47 ill persons
with an average age of (09±06 ) years , with whom the disease has
diagnosed by blood and marrow examination in the hospital of blood
diseases in the CHU of Batna, and on 194 healthy witnesses of the
same age. The two groups were benefited by a dosage of the
concentration of the homocysteine vitamin B9 ,vitamin B12 , and
also of the study of special polymorphisms of indispensable enzymes
in the metabolism of this acid , and that by the use of the method (
Light cycler ) Real time PCR , on the following enzymes : MS (
C2756G ), MSR ( A66G ) ,MTHFR1 ( C677T ) and MTHFR2
(A1298C). The obtained results have revealed that the rate of the
homozygote muted genotype is the less frequent in the two groups ,
and that exist at list one genotype of each enzyme in the ill group and
in which the percentage exceed with remarkable way the same
genotype in the healthy group and we notice specially the muted
genotype GG of -the methionine synthetase-and the form TT of the
enzyme – methyline tetra hydrofolate reductase – We notice the
existence of considerable number of genotypes in the ill group lied
with characteristic increase of this Amino-acid ,and that for the
reduction of the biologic activity of these enzymes which become
inefficient in the transfer of the homocysteine into the methionine
and cause the diminution of the biologic activity of these enzymes
and with consequence the reduction of the percentage of methylic
radicals in the DNA of studied genes and that lead to the increase of
the activity and the capacity of transcription , and it-s so probably
that this last one is one of the factors of this disease especially if we
know that the specific check-up of vitamins is normal and similar in
the two groups , which ovoid the hypothesis of the reduction of
vitamins . We notice also that the heterozygote genotype is the less in
the sick category except the MTHFR2. Wild genotype is more
frequent in the witness group except MSR. Even these results are
partials; they open a new way in the genetic diagnosis of this
malicious disease which allow a precocious diagnosis and the use of
an effective and appropriated treatment in the same time.
[1] S. Diop, R. Letestu , D. Orsolani, and Y. Lebouef ," Expression of
proliferation marker Ki 67 in chroniclymphocyticleukimea". Dakar
medical. Vol. 50, no. 2, pp. 65-8, 2005.
[2] J.B Dubois, « Les marqueurs tumoraux sériques De la théorie ├á la
pratiqu e ». Montpellier Edition Espace . 1996.
[3] Y. Fulla, F. ana pycha,.. "Place des marqueurs tumoraux circulants
dans la diagnostic et le suivie des tumeurs clorectales » . MédNucl Vol.
20, pp. 269-75, 1996.
[4] ] H. Zetterberg, B.Regland, M.Palmer, A.Ricksten, L.Plmqvist, and
L.Rymo,"Increased frequency of combined methyl ntetre hydrofolate
reductase C677Tand A1298C mutated allales in spontan,e
ousabortedembros". Eur J Hum Genet, Vol. 10, pp. 113-8, 2002.
[5] ] PM.Ueland , S. Hustad. and J.Schneed ,"Biological and clinical
implication of the MTHFR C677T polymorphism".Trends Pharmacol
Sci, Vol. 22, pp. 269-272, 2001.
[6] R.F. Franco, A.G. Argio, J.F. Guerreiro, J. Elion And M.A. Zago,
"Analysis of the C677T mutation of the methyl netetra hydrofolate
reductase Gene in defferente thnic groups" .ThrombHeamost, Vol. 79,
pp. 119-121, 1998.
[7] E. Ruud, H. Holmstrom, F.Brosstad, and F. Wesenberg. "Children with
acute lymphoblastic Leukemia have high plasma levels of total
homocysteineat time of diagnosis". Scandivian J Clin and Lab
Invest,Vol. 66, no. 1, pp. 67-78, 2006.
[8] D.Valik, J.Sterba, V. Bajciova, and R.Demlova , "Severe
encephalopathy induced by the first but not the second course of highdose
methotrexate mirrored by plasma homocysteine elevation and
preceded by externe differences in pretreatment plasma folate
.Oncology, Vol. 69, no. 3, pp. 269-272, 2005.
[9] J.Sterba, L.Dusek, R. Demlova, and D.Valik, "Pretreatment plasma
folate modulates the pharmacodynamic effect of high-dose methotrexate
in children with acute lymphoblastic Leukemia and non-Hodgkin
lymphoma : folateoverrescue concept revisited" .Clin Chem,Vol. 52,
no. 4, pp. 692-700. 2006.
[10] D.J. Gaughan, S. Barbaux, L.A. Kluijtmans, and A.S. Whitehead, "The
human and mouse Methylenetetrahydrofolatereductase (MTHFR)
genes : genomic organisation , mRNA structure and linkage to the
CLCN6 gene" , Gene , Vol. 257, pp. 279-89. 2000.
[11] J .Geisel, L. Zimblemann , H. Schorr, J.P. Knapp, M. Bodies, U.
Hubner, and W.Hermann, "Genetic defects as important factor for
moderate hyperhomocysteinema" .Clin ChemLab Med,Vol. 39, pp. 698-
704. 2001.
[12] S. Kishi, J. Griener , c.,Cheng , Das, E. Cook, D. Pei, M. Hudson, J.
Rubnitz, and J. T. "Sandlund, Homocysteine, pharmacogenetics,
andneurotoxicity in children with Leukemia" . J Clin Oncology, Vol.
21, no. 16, pp. 3084-3091, 2003.
[13] K . Boduroglu, Y. Alanay , B. Koldan , and E. Tunbilek ,
"Methylenetetra hydrofolate reductase enzyme polymorphisms as
maternalrisk for Down syndrome among Turkish women" . Am J Med
Genet , Vol. 127, pp. 5-10. 2004 .
[1] S. Diop, R. Letestu , D. Orsolani, and Y. Lebouef ," Expression of
proliferation marker Ki 67 in chroniclymphocyticleukimea". Dakar
medical. Vol. 50, no. 2, pp. 65-8, 2005.
[2] J.B Dubois, « Les marqueurs tumoraux sériques De la théorie ├á la
pratiqu e ». Montpellier Edition Espace . 1996.
[3] Y. Fulla, F. ana pycha,.. "Place des marqueurs tumoraux circulants
dans la diagnostic et le suivie des tumeurs clorectales » . MédNucl Vol.
20, pp. 269-75, 1996.
[4] ] H. Zetterberg, B.Regland, M.Palmer, A.Ricksten, L.Plmqvist, and
L.Rymo,"Increased frequency of combined methyl ntetre hydrofolate
reductase C677Tand A1298C mutated allales in spontan,e
ousabortedembros". Eur J Hum Genet, Vol. 10, pp. 113-8, 2002.
[5] ] PM.Ueland , S. Hustad. and J.Schneed ,"Biological and clinical
implication of the MTHFR C677T polymorphism".Trends Pharmacol
Sci, Vol. 22, pp. 269-272, 2001.
[6] R.F. Franco, A.G. Argio, J.F. Guerreiro, J. Elion And M.A. Zago,
"Analysis of the C677T mutation of the methyl netetra hydrofolate
reductase Gene in defferente thnic groups" .ThrombHeamost, Vol. 79,
pp. 119-121, 1998.
[7] E. Ruud, H. Holmstrom, F.Brosstad, and F. Wesenberg. "Children with
acute lymphoblastic Leukemia have high plasma levels of total
homocysteineat time of diagnosis". Scandivian J Clin and Lab
Invest,Vol. 66, no. 1, pp. 67-78, 2006.
[8] D.Valik, J.Sterba, V. Bajciova, and R.Demlova , "Severe
encephalopathy induced by the first but not the second course of highdose
methotrexate mirrored by plasma homocysteine elevation and
preceded by externe differences in pretreatment plasma folate
.Oncology, Vol. 69, no. 3, pp. 269-272, 2005.
[9] J.Sterba, L.Dusek, R. Demlova, and D.Valik, "Pretreatment plasma
folate modulates the pharmacodynamic effect of high-dose methotrexate
in children with acute lymphoblastic Leukemia and non-Hodgkin
lymphoma : folateoverrescue concept revisited" .Clin Chem,Vol. 52,
no. 4, pp. 692-700. 2006.
[10] D.J. Gaughan, S. Barbaux, L.A. Kluijtmans, and A.S. Whitehead, "The
human and mouse Methylenetetrahydrofolatereductase (MTHFR)
genes : genomic organisation , mRNA structure and linkage to the
CLCN6 gene" , Gene , Vol. 257, pp. 279-89. 2000.
[11] J .Geisel, L. Zimblemann , H. Schorr, J.P. Knapp, M. Bodies, U.
Hubner, and W.Hermann, "Genetic defects as important factor for
moderate hyperhomocysteinema" .Clin ChemLab Med,Vol. 39, pp. 698-
704. 2001.
[12] S. Kishi, J. Griener , c.,Cheng , Das, E. Cook, D. Pei, M. Hudson, J.
Rubnitz, and J. T. "Sandlund, Homocysteine, pharmacogenetics,
andneurotoxicity in children with Leukemia" . J Clin Oncology, Vol.
21, no. 16, pp. 3084-3091, 2003.
[13] K . Boduroglu, Y. Alanay , B. Koldan , and E. Tunbilek ,
"Methylenetetra hydrofolate reductase enzyme polymorphisms as
maternalrisk for Down syndrome among Turkish women" . Am J Med
Genet , Vol. 127, pp. 5-10. 2004 .
@article{"International Journal of Medical, Medicine and Health Sciences:50425", author = "Yahia Massinissa and Kalla A and Yahia M and Benbia S", title = "Genetic Polymorphism of the Acute Lymphoblastic Leukaemia and Hyperhomocysteinemia its Relation with the for a Group of Children in the East of Algeria", abstract = "A lot of recent research have spoken on the relation
between the increase of the homocysteinemia and some kinds of
cancer . For that, our study was based on the research of a possible
relation between the increase of the concentration of this amino-acid
in the plasma and the appearance of the disease of the Acute
Lymphoblastic Leukaemia in a part of Algerian children with Berber
origin in the East of Algeria . The study has done on 47 ill persons
with an average age of (09±06 ) years , with whom the disease has
diagnosed by blood and marrow examination in the hospital of blood
diseases in the CHU of Batna, and on 194 healthy witnesses of the
same age. The two groups were benefited by a dosage of the
concentration of the homocysteine vitamin B9 ,vitamin B12 , and
also of the study of special polymorphisms of indispensable enzymes
in the metabolism of this acid , and that by the use of the method (
Light cycler ) Real time PCR , on the following enzymes : MS (
C2756G ), MSR ( A66G ) ,MTHFR1 ( C677T ) and MTHFR2
(A1298C). The obtained results have revealed that the rate of the
homozygote muted genotype is the less frequent in the two groups ,
and that exist at list one genotype of each enzyme in the ill group and
in which the percentage exceed with remarkable way the same
genotype in the healthy group and we notice specially the muted
genotype GG of -the methionine synthetase-and the form TT of the
enzyme – methyline tetra hydrofolate reductase – We notice the
existence of considerable number of genotypes in the ill group lied
with characteristic increase of this Amino-acid ,and that for the
reduction of the biologic activity of these enzymes which become
inefficient in the transfer of the homocysteine into the methionine
and cause the diminution of the biologic activity of these enzymes
and with consequence the reduction of the percentage of methylic
radicals in the DNA of studied genes and that lead to the increase of
the activity and the capacity of transcription , and it-s so probably
that this last one is one of the factors of this disease especially if we
know that the specific check-up of vitamins is normal and similar in
the two groups , which ovoid the hypothesis of the reduction of
vitamins . We notice also that the heterozygote genotype is the less in
the sick category except the MTHFR2. Wild genotype is more
frequent in the witness group except MSR. Even these results are
partials; they open a new way in the genetic diagnosis of this
malicious disease which allow a precocious diagnosis and the use of
an effective and appropriated treatment in the same time.", keywords = "Genetic polymorphism, Acute Lymphoblastic
Leukaemia, Biomarkers, Metabolism of homocystein", volume = "6", number = "3", pages = "44-3", }