The AML1 gene encoding the DNA-binding -subunit in the Runt domain family of heterodimeric transcription factors has been noted for its frequent involvement in chromosomal translocations associated with leukemia. Using reverse transcriptase-polymerase chain reaction (RT-PCR) combined with nonisotopic RNase cleavage assay (NIRCA), we found point mutations of the AML1 gene in 8 of 160 leukemia patients: silent mutations, heterozygous missense mutations, and biallelic nonsense or frameshift mutations in 2, 4, and 2 cases, respectively. The mutations were all clustered within the Runt domain. Missense mutations identified in 3 patients showed neither DNA binding nor transactivation, although being active in heterodimerization. These defective missense mutants may be relevant to the predisposition or progression of leukemia. On the other hand, the biallelic nonsense mutants encoding truncated AML1 proteins lost almost all functions examined and may play a role in leukemogenesis leading to acute myeloblastic leukemia.
Thailand is now faced with a double burden of malnutrition. Using nationally representative data from the 2015–2016 Multiple Indicator Cluster Survey, we utilized multinomial logistic regression models to examine factors associated with stunting only, wasting only, overweight only, concurrent stunting and overweight, and concurrent stunting and wasting among children 0–59 months of age (
n
= 11,068). The prevalences of <5 stunting only (height‐for‐age
Z
score < −2 SD) and wasting only (WHZ < −2 SD) were 8.5% and 4.7%, respectively. The prevalence of <5 overweight only (WHZ > +2 SD) was 7.8%. Children 12–23 months (risk ratio [RR], 95% confidence interval [CI]: 1.47 [1.18, 1.83];
p
< .01) and 24–35 months (RR, 95% CI: 1.56 [1.26, 1.94];
p
< .001) were at increased risk for stunting only, compared with children 48–59 months. The strongest risk factor for stunting only was low birth weight (RR, 95% CI: 3.42 [2.86, 4.10];
p
< .001). Children 0–5 months were at highest risk for wasting only, compared with children 48–59 months (RR, 95% CI: 2.91 [2.16, 3.92];
p <
.001). Children 48–59 months and male children were more likely to be overweight only. Higher household wealth and smaller household size were also significant predictors of overweight only. A small proportion of children were concurrently stunted and overweight (1.3%) and concurrently stunted and wasted (0.6%). A multipronged approach focused on adequate prenatal care, improving breastfeeding and complementary feeding practices, and mitigating the growing burden of overweight is needed to address the double burden of malnutrition in Thailand.
Summary. We examined deletion and methylation of the p15 INK4B (p15) and p16 INK4A (p16) genes, using Southern blotting and methylation-specific polymerase chain reaction (PCR), in 70 untreated adult patients with precursor B-cell acute lymphoblastic leukaemia (PBC-ALL) and analysed the relationship between their genetic changes and clinical outcome. Methylation and homozygous deletion of the p15 gene were detected in 30 (43%) and 18 (26%) patients, while those of the p16 gene were found in 16 (23%) and 11 (16%) patients respectively. Thirteen out of 17 patients with wild-type p15 gene showed expression of p15 mRNA, whereas 31 out of 39 patients with alteration (deletion and methylation) of the p15 gene showed no p15 mRNA expression by reverse transcription-PCR, suggesting that alterations of the p15 gene are highly associated with loss of p15 mRNA expression. Disease-free survival (DFS) at 4 years in patients with wild-type p15 gene is 33%, compared with 4% of those with p15 gene alterations (P ¼ 0AE049). Multivariate analysis showed that the absence of p15 gene alterations was an independent significant favourable prognostic factor for longer DFS (P ¼ 0AE0001). These results suggest that alterations in the p15 but not p16 gene can be used as a genetic prognostic indicator in PBC-ALL.
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