Personalized Treatment of 6-Mercaptopurine in Thai Children with Acute Lymphoblastic Leukemia

Thanks to its ability to inhibit deoxyribonucleic acid synthesis, 6-mercaptopurine (6-MP), is one of the indispensable medications for acute lymphoblastic leukemia (ALL) patients. Nevertheless, some patients may succumb to myelotoxicity, leading to treatment disruption or even life-threatening events. Owing to the advances in pharmacogenomics, the genetic polymorphism of genes regulating purine synthesis has been identified and physicians can adjust the dose of 6-MP according to each polymorphism. Such polymorphisms genetically vary among ethnicities. In this article, 2 genetic polymorphisms, namely thiopurine methyltransferase and Nudix (nucleoside diphosphate linked moiety X) type motif 15, are clinically discussed, with a special focus on the clinical studies in Thai children with ALL.

Successful Sublingual Cobalamin Treatment in a Child with Short-Bowel Syndrome

Vitamin B12 (B12) is essential for deoxyribonucleic acid synthesis, to maintain normal hematologic and neurologic functions. Studies suggest that cobalamin deficiency in children is more common than previously recognized. Main causes are decreased intake, abnormal absorption, and inborn errors of metabolism. The classic treatment for cobalamin deficiency is intramuscular administration of B12. There are no data concerning the use of alternative routes of cobalamin administration in children. This report shares the experience of sublingual administration of B12 to a patient with short-bowel syndrome and B12 malabsorption. We report the case of successful treatment of cobalamin deficiency by sublingual administration in a 9-year-old patient who had undergone intestinal resection and jejunum-colon, with anastomosis of 32 cm of residual small intestine and absence of distal jejunum and ileocecal junction. We determined a B12 deficiency because low serum cobalamin levels (<200 pg/mL) were shown in 2 consecutive tests (130 pg/mL and 170 pg/mL). The patient presented with neither clinical nor hematological manifestations. He received sublingual cobalamin preparation, 1000-mcg sublingual nuggets per day for 1 month. Normalization of serum cobalamin was obtained (790 pg/mL) after 1 month of treatment. The sublingual route of administration not only improved the quality of life of this patient by avoiding monthly painful injections but also reduced the cost of treatment and the number of hospital visits.

Overexpression of Activin βC or Activin βE in the Mouse Liver Inhibits Regenerative Deoxyribonucleic Acid Synthesis of Hepatic Cells

Activins are dimeric growth factors composed of β-subunits, four of which have been isolated so far. Whereas activin βA and βB are expressed in many tissues, the expression of activin βC and βE is confined to the liver. To date no biological role or activity has been assigned to activins formed from βC or βE subunits (activin C and E). Because activin A (βAβA), among its various functions in other tissues, appears to be a negative regulator of liver growth, we hypothesized a similar role for activin C and E. Using a nonviral gene transfer system we specifically delivered genes encoding activin βC, βE, or βA to the mouse liver. The mRNA analysis and reporter gene coexpression both indicated a reproducible temporal and spatial transgene expression pattern. The effects of activin overexpression were studied in the context of a regenerative proliferation of hepatic cells, a result of the tissue damage associated with the hydrodynamics based gene transfer procedure. Activin βC, βE, or βA expression, all temporarily inhibited regenerative DNA synthesis of hepatocytes and nonparenchymal cells, though to a varying degree. This first report of a biological activity of activin C and E supports an involvement in liver tissue homeostasis and further emphasizes the role of the growing activin family in liver physiology.