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1.
J Egypt Natl Canc Inst ; 20(2): 111-20, 2008 Jun.
Article in English | MEDLINE | ID: mdl-20029466

ABSTRACT

BACKGROUND: Cell-marker profiling has led to conflicting conclusions about its prognostic significance in T-ALL. AIM: To investigate the prevalence of the expression of CD34, CD10 and myeloid associated antigens (CD13/ CD33) in childhood T-ALL and to relate their presence to initial clinical and biologic features and early response to therapy. PATIENTS AND METHODS: This study included 67 consecutive patients with newly diagnosed T-ALL recruited from the Children's Cancer Hospital in Egypt during the time period from July 2007 to June 2008. Immunophenotypic markers and minimal residual disease (MRD) were studied by five-color flow cytometry. RESULTS: The frequency of CD34 was 34.9% , CD10 33.3% , while CD13/CD33 was 18.8%. No significant association was encountered between CD34, CD10 or myeloid antigen positivity and the presenting clinical features as age, sex, TLC and CNS leukemia. Only CD10(+) expression had significant association with initial CNS involvement (p=0.039). CD34 and CD13/CD33 expression was significantly associated with T-cell maturation stages (p<0.05). No relationship was observed for age, TLC, gender, NCI risk or CNS involvement with early response to therapy illustrated by BM as well as MRD day 15 and day 42. CD34(+), CD13/CD33(+) and early T-cell stage had high MRD levels on day 15 that was statistically highly significant (p<0.01), but CD10(+) had statistically significant lower MRD level on day 15 (p=0.049). However, only CD34 retained its significance at an MRD cut-off level of 0.01%. CONCLUSIONS: CD34, CD10, CD13/CD33 expression, as well as T-cell maturation stages, may have prognostic significance in pediatric T-ALL as they have a significant impact on early clearance of leukemic cells detected by MRD day 15.


Subject(s)
Biomarkers, Tumor/metabolism , Neoplasm, Residual/diagnosis , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adolescent , Antigens, CD/metabolism , Antigens, CD34/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , CD13 Antigens/metabolism , Cell Differentiation , Child , Child, Preschool , Egypt , Female , Flow Cytometry , Humans , Immunophenotyping , Infant , Male , Neoplasm, Residual/metabolism , Neoplasm, Residual/therapy , Neprilysin/metabolism , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Prognosis , Remission Induction , Sialic Acid Binding Ig-like Lectin 3 , Treatment Outcome
2.
J Med Genet ; 44(6): 363-7, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17220211

ABSTRACT

BACKGROUND: A 776C-->G variant (dbSNP ID: rs1801198) in the transcobalamin gene (TCN2; MIM# 275350) decreases the cellular and plasma concentration of transcobalamin and thereby influences the cellular availability of vitamin B(12). OBJECTIVE: To evaluate the worldwide prevalence of this variant and its association with homocysteine plasma level. METHODS: The study was performed in 1433 apparently healthy subjects, including Afro-Americans and Afro-Africans and in 251 Afro-Africans participants with severe malaria. RESULTS: The frequencies of the 776G allele were the highest in China (0.607; 95% CI 0.554 to 0.659), low in West Africa (Bénin and Togo, 0.178; 0.154 to 0.206), and intermediate in France (0.445; 0.408 to 0.481), Italy (0.352; 0.299 to 0.409), Morocco (0.370; 0.300 to 0.447) and Mexico (0.374; 0.392 to 0.419). The 776G genotype was more frequent in Afro-Americans from New York (16.7; 8.4 to 30.7) and in Afro-African patients with severe malaria (6.0%; 95% CI 3.7 to 9.6) than in healthy Afro-African volunteers (p = 0.0004 and p = 0.033, respectively), while no difference was observed for MTHFR 677TT and 677T alleles. A disequilibrium of TCN2 genotype distribution was recorded in patients with severe malaria, with a twofold higher GG genotype than expected (p = 0.010). An association between the TCN2 polymorphism and homocysteine was observed only in Mexico and France, the two countries with the highest rate of low plasma concentration of vitamin B(12) (<100 pmol/l). CONCLUSION: Given the dramatic heterogeneity of the 776G allele frequency worldwide, this polymorphism may be prone to a selective pressure or confers an evolutionary advantage in confronting environmental factors, one of which is malaria.


Subject(s)
Cytosine , Environment , Gene Frequency/genetics , Guanine , Mutation/genetics , Transcobalamins/genetics , Adult , Genotype , Homocysteine/blood , Humans , Linkage Disequilibrium/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Middle Aged
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