We report the sublocalization of the breakpoint in chromosome 22 in 33 patients with chronic myeloid leukemia (CML) who also had unusual marrow cytogenetics. In 23 patients, the leukemic clones were characterized by Philadelphia (Ph1) chromosomes that arose through complex translocations that involved three or more chromosomes. In the remaining ten patients, there were no detectable Ph1 chromosomes despite molecular evidence for the presence of rearrangements in the major breakpoint cluster region (bcr) of chromosome 22 in all cases. There was no significant difference between the two groups with respect to location of the breakpoints within the bcr. When these two groups of patients were combined, there was a significant excess of breakpoints in one segment of the bcr when compared to the distribution of breakpoints seen in 119 patients with simple 9;22 translocations. The difference in breakpoint distributions did not appear to be entirely attributable to differences between groups in disease duration at the time of study. These data support the notion that the unusual genetic recombinations that give rise to BCR/ABL fusion genes in CML involve specific DNA sequences of BCR (and possibly ABL) and additional, recombinogenic sequences, at least some of which are present in loci known to be nonrandomly involved in complex Ph1 translocations.

Adult↗

PubMed1989

Restriction fragment length polymorphism analysis of hematopoietic cells following successful treatment of relapsed acute lymphoblastic leukemia following bone marrow transplantation.

Despite aggressive therapy for leukemia in the form of bone marrow transplantation (BMT) relapse occurs in a significant number of cases. The origin of the leukemic relapse, whether it is of donor or recipient origin, and how best to treat the patients continue to pose problems for the clinician. In this paper we present a case in which the cytogenetics suggested that the relapse was of donor origin; however, molecular analysis revealed that the leukemic population was of host origin. The leukemic relapse following the BMT was treated with a second BMT. This resulted in a remission of 28 months after which leukemic relapse was again diagnosed. Using conventional chemotherapy it was possible to obtain another complete remission. This case illustrates a pitfall to cytogenetic analysis and two contrasting methods of dealing with leukemic relapse following BMT.

Adult↗

PubMed1989

A study of the menopause, smoking, and contraception in women with Crohn's disease.

One hundred and ninety-six women with Crohn's disease from south-east Wales were asked to provide details of their menstrual cycles, age at menopause, history of surgery, smoking habits and use of oral contraceptives. One hundred and forty-six provided the information (response rate 77 per cent). Eighty-four were still menstruating, three were pregnant, 10 had undergone hysterectomy, one had a pharmacologically-induced menopause and 48 had had a physiological menopause. Of these 48 women, 33 were diagnosed as having Crohn's disease before the menopause. Twenty-five of these were smokers. The mean age at menopause was similar in smokers and non-smokers and in those diagnosed before and after the menopause. The mean age at menopause was between 46 and 47. A logistic analysis using the 'status quo' method showed that 50 per cent of women with Crohn's disease had the menopause at 47.6 years compared with 49.6 years in a group of healthy women from the same area. The two groups had similar smoking habits and it would seem that a premature menopause is associated with Crohn's disease.

Adult↗

PubMed1988

Isolation and properties of cDNA clones encoding SRF, a transcription factor that binds to the c-fos serum response element.

The serum response element (SRE) is a sequence required for transient transcriptional activation of genes in response to growth factors. We have isolated cDNA clones encoding serum response factor (SRF), a ubiquitous nuclear protein that binds to the SRE. The SRF gene is highly conserved through evolution, and in cultured cells its transcription is itself transiently increased following serum stimulation. A cDNA clone of SRF expressed in vitro generates protein that forms complexes indistinguishable from those formed with HeLa cell SRF, as judged by DNA binding specificity and the ability to promote SRE-dependent in vitro transcription. SRF binds DNA as a dimer, and the DNA binding/dimerization domain of the protein exhibits striking homology to two yeast regulatory proteins.

Base Sequence↗

PubMed1988