Reverse transcription polymerase chain reaction was used to detect an unusual BCR/ABL transcript in a patient who presented with thrombocythaemia and was Philadelphia chromosome positive but weakly reactive to conventional BCR/ABL fusion probes. Sequencing revealed the presence of a 12 bp insert between BCR exon2 (b2) and ABL exon2 (a2). In such cases the use of conventional BCR/ABL probes may lead to false negative results. This is the first report of this transcript. Clinically the patient has responded well to therapy.
Serum alpha-fetoprotein levels rise during various stages of poisoning of baboons with diethylnitrosamine before the induction of any liver tumours. The possible mechanisms causing raised AFP levels in people ,from primary liver cancer high-risk areas are discussed in the light of these experimental toxicity studies on baboons.Few chemical agents besides diethylnitrosamine (DENA) can cause primary liver cancer (PLC) in primates. Hull, O'Gara, Kelly and their group produced tumours fairly regularly and were able to subculture the liver tumours (Hull et al., 1969). A relatively insensitive test for alphafetoprotein (AFP) was used so that the presence of AFP in the serum was a fairly late manifestation of the induced tumours in their monkeys.Since little was known at the time of the AFP response in human hepatic disease other than its appearance in certain liver and other tumours (Abelev, 1971) and the tendency for the levels of AFP in sick neonates to remain high or increase (Hull et al., 1969; Masopust et al., 1971 ; Purves et al., 1970a), DENA was administered to baboons to determine the response to a known toxic stimulus and to perhaps induce PLC in the animals. The study has now run 3 years. MATERIAL AND METHODSYoung baboons of both sexes were used with a range of ages from neonatal (1.6 kg) to older (8 kg). Three baboons were started on intraperitoneal DENA (20 mg/kg) administered every 2 weeks (Hull et al., 1969). After five intraperitoneal doses this was changed to 5 mg/kg DENA, orally, three times a week administered on bread before the main feed of the day. Consumption was very complete and volatilization of the DENA was thereby avoided. The intraperitoneal route was abandoned as eight Cercophithecus monkeys given the same dose all died of acute yellow atrophy of the liver. All subsequent animals were given DENA by the oral route. Since long-term survival was one of the main objectives of the study very careful attention was paid to biochemical parameters and the clinical condition of the animals that could indicate deterioration. Past experience of toxicity studies on young baboons has indicated that weight decreases have a serious connotation. Whenever one or more animals began to show weight-loss the treatment of that batch of animals was halted and recommenced later when the deficiency in weight gain had been corrected. Older animals and the same animals in subsequent treatment spells, were more resistant and this effect was less pronounced; nevertheless the interrupted regimes were continued.The animals were bled from the femoral vein, weighed at regular intervals and members of the groups were biopsied at various stages. Either phencyclidine hydrochloride (Parke-Davis) or diethyl ether were used to anaesthetize the animals.Initially many biochemical parameters were studied but latterly only serum alkaline phosphatase has been assayed since this has consistently shown the most marked changes. The alkaline phosphatase isoenzyme pattern during an in-
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