Intellectual functioning of childhood leukemia survivors - relation to Tau protein - a marker of white matter injury

PurposeChemo- and radiotherapy used in acute lymphoblastic leukemia (ALL) can influence on brain functioning in the future. In a prospective study we analysed the cognitive functions of ALL survivors in relation to Tau protein as a marker of white matter injury.Material and methodsThirty-one survivors of childhood ALL (6.3 years after diagnosis); without the signs of CNS involvement, treated with chemotherapy alone, rested in first remission; underwent Intelligence tests- Wechsler Intelligence Scales (WISC-R, WAIS-R). Their results were analyzed in relation to the levels of Tau in cerebrospinal fluid (CSF) obtained during the treatment.ResultsThe analysis showed that all survivors attained the average scores in intelligence tests. A negative correlation was found between methotrexate (MTX) doses and Freedom from Distractibility (FFD). Females had higher values of Performance Intelligence Quotient (PIQ) than males. A negative correlation was noted of Tau protein levels obtained from the last CSF with: Total and Verbal Intelligence Quotient, PIQ, Perceptual Organisation Index and FFD but not with Verbal Comprehension Index.ConclusionOur results suggest the possibility of white matter injury during the treatment for ALL with chemotherapy alone. Elevated Tau protein level in CSF at the end of treatment might indicate future difficulties in neurocognitive functioning.     

Haemoglobin Constant Spring has an unstable α chain messenger RNA

Haemoglobin Constant Spring (Hb CS) is a variant with an elongated α-chain associated with an α⁺ thalassaemia phenotype. The amount of α mRNA relative to β mRNA in reticulocytes was reduced in carriers of Hb CS by an amount equivalent to the reduction observed in carriers of α⁺ thalassaemia. In a patient with Hb CS-H disease there was greater α/β mRNA ratio in bone marrow nuclear RNA than in the peripheral blood. Furthermore, all the α mRNA in the patient's peripheral blood was derived from the α1 (α^A) gene. The data suggest that α^CS mRNA is unstable and degraded in the cytoplasm. This instability may be due to destabilization of a specific sequence in the 3'non-coding region during translation.     

Genetic control of F cells in human adults.

Hb F levels were determined on samples from 750 normal blood donors. Six individuals (0.8%) had Hb F levels in excess of 1.1%, the upper end of the continuous distribution. Eight individuals at the upper end and 7 individuals at the lower end of the range were selected for family studies. These studies revealed that the control of Hb F levels in adults, as judged by the more sensitive F-cell technique, has a major genetic component. Structural analysis of the Hb F in several cases demonstrated that both G gamma and A gamma chains were present, but in variable proportions. These results are discussed in light of current concepts of adult F-cell production.     

Occurrence of Gγ Hb F in Greek HPFH: Analysis of Heterozygotes and Compound Heterozygotes with β Thalassaemia

Haemoglobin F has been isolated from the red cells of individuals with the Greek form of hereditary persistence of fetal haemoglobin (HPFH), and the glycine/alanine composition of the gamma CB3 peptides determined. In contrast to previous reports we have shown that the Hb F of the Greek HPFH heterozygotes contains significant amounts of G gamma chains and circumstantial evidence indicates that these are the products of the same chromosome that carries the Greek HPFH determinant. Hence this chromosome must be directing the synthesis of G gamma, A gamma and (probably) beta and delta chains, thus implying that the Greek form of HPFH does not result from a deletion involving the globin chain structural genes. Analysis of the levels and structure of Hb F from the Greek HPFH heterozygotes and from separated cell populations from the Greek HPFH/beta thalassaemia compound heterozygotes indicate that the Greek HPFH determinant, while allowing an overall increase in gamma chain synthesis, is not the sole factor determining the absolute amount of Hb F production on a cellular basis.