No abstract

The t(6;9) associated with a subtype of acute myeloid leukemia (AML) was shown to generate a fusion between the 3' part of the CAN gene on chromosome 9 and the 5' part of the DEK gene on chromosome 6. The same part of the CAN gene appeared to be involved in a case of acute undifferentiated leukemia (AUL) as well, where it was fused to the SET gene. Genomic sequences around the translocation breakpoint were determined in two t(6;9) samples and in the case of the SET-CAN fusion. Although coexpression of myeloid markers and terminal deoxynucleotidyl transferase was shown to be one of the characteristics of t(6;9) AML, no addition of random nucleotides at the translocation breakpoint could be found. In addition, the breakpoint regions did not reveal heptamer-nonamer sequences, purine-pyrimidine tracts, a chi-octamer motif, or Alu repeats. The sequence in which the translocation breakpoints occurred was enriched in A/T. Notably, the specific introns in which clustering of breakpoints occurs in DEK and CAN both contain a LINE-I element. As LINE-I elements occur with a moderate frequency in the human genome, the presence of such an element in both breakpoint regions may be more than coincidental and may play a role in the translocation process.

The commonly used rapid infusion rate (A) of FeGl causes 'oversaturation' of transferrin. This is compatible with iron toxicity due to free iron which may explain our patients' complaints. Free iron cannot be measured directly. LDH as a crude measure of cell damage was not elevated. Better measurements to prove free iron toxicity, like lipid peroxides, are not yet readily available. Infusion during a longer period at a lower dose (D) is effective and eliminates 'Oversaturation' of transferrin and probably the danger of iron toxicity.

HoloTC has a better diagnostic accuracy than vitamin B(12) and can replace the existing vitamin B(12) assay as a primary screening test in patients suspected of vitamin B(12) deficiency. Critical evaluation of cut-off values of holoTC indicated that a cut-off value of 32 pmol/L can be considered in screening for metabolic vitamin B(12) deficiency (defined by MMA > 0.45μmol/L) in a mixed patient population.

Summary. To investigate whether the different pharmacokinetics of acenocoumarol (t 1/2 ¼ 11 h) and phenprocoumon (t 1/2 ¼ 140 h) result in a different quality of anticoagulation, we studied patients from the Leiden anticoagulation clinic treated between 1998 and 1999 for more than 16 weeks. Two hundred and twenty-eight pairs were closely matched for indication for oral anticoagulant therapy (OAT), age, sex and date of start of treatment. Four hundred and fifty six patients with 7245 International Normalized Ratio (INR) checks yielded 230 patient-years. Quality of OAT calculated over the whole treatment period was higher with phenprocoumon as expressed by the number of INR checks in the therapeutic range (phenprocoumon: 42AE7%, acenocoumarol: 36AE5%, difference: 6AE1%, CI 95 of the difference: 3AE0-9AE3%) and by time in range (phenprocoumon: 46AE6%, acenocoumarol: 41AE6%, difference: 5AE0%, CI 95 of the difference: 1AE3-8AE6%). After the initial 6 weeks of OAT, the differences became more pronounced (difference: 6AE1%, CI 95 : 1AE8-10AE4%). The incidence of severe bleeding complications was similar (phenprocoumon: 0AE04/patient/year vs acenocoumarol: 0AE03/patient/ year) with a slight excess of minor bleeds with phenprocoumon (0AE19/patient/year vs 0AE06/patient/year). We conclude that phenprocoumon leads to a better quality of OAT than acenocoumarol. As there is no difference in major bleeding complications and only a small difference in minor bleeding complications, phenprocoumon is preferable to acenocoumarol for prolonged OAT.