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The Philadelphia (Ph) chromosome is a small chromosome 22, which results from a reciprocal translocation between the long arms of chromosome 9 and 22, designated t (9;22) (q34;q11). It was first described in association with chronic myeloid leukaemia (CML), where 90% of cases examined are Ph-positive. A similar cytogenetic abnormality has also been identified in the acute leukaemias but in a much lower percentage. The ubiquitous nature of the translocation in CML suggested that it was causally implicated in the pathogenesis of the disease. Recent work at the molecular level has corroborated this idea. As a consequence of the translocation, the Abelson protooncogene (ABL), located on chromosome 9 is moved to chromosome 22 where it is joined to a truncated gene, known as BCR. The result of this genomic reorganisation is a hybrid gene encoding a novel chimaeric protein product with enhanced protein tyrosine kinase activity. It is thought that it is this activity which is necessary for the generation of the leukaemic phenotype. The t(9;22) has provided a model to illustrate how cellular proto-oncogenes can be activated by chromosomal translocation and has stimulated interest in investigating other chromosomal translocations in human malignancies.

Seven patients with Philadelphia (Ph) chromosome positive essential thrombocythemia (ET) were investigated for the presence of a rearrangement within the major breakpoint cluster region (M-bcr) using the Southern blot technique and, in six cases, for the presence of the hybrid bcr-abl mRNA using the polymerase chain reaction (PCR). The molecular studies showed rearrangement of M-bcr in all cases; there was evidence of the b2a2 mRNA junction in one case and of b3a2 junction in five cases. These findings are identical to what might have been expected in Ph-positive chronic myeloid leukemia. These features may explain the poor prognosis of Ph-positive ET in comparison with cytogenetically normal cases. Conversely, the differences in clinical presentation may be due to other genetic changes.

The occasional finding of cells positive for the Philadelphia (Ph) chromosome months or years after bone-marrow transplantation for chronic myeloid leukaemia raises the possibility that the Ph-positive clone may never be eradicated. The polymerase chain reaction with probes able to detect the transcript of the bcr/abl hybrid gene at very low levels was used to study marrow cells from seven patients in continuing haematological and cytogenetic remission 5-7 years after allogeneic bone-marrow transplantation for chronic myeloid leukaemia. No evidence of the leukaemic mRNA was found. Thus, it seems that all leukaemic cells were eradicated in these patients and that they are truly cured.

The relationship between platelet size and platelet count was investigated in 41 patients with Crohn's disease. A high platelet count was associated with a decrease in platelet size, but an overall increase in the platelet crit. There was also a significant correlation between the patient's platelet count and serum orosomucoids, which have traditionally been used to assess disease activity.