F.W. Gunz

A cytogenetic study of eight human melanoma cell lines

&NA; Eight cell lines established originally at the Queensland Institute of Medical Research from human malignant melanoma explants have been studied by means of cytogenetic techniques. All showed abnormalities characteristic for each individual line and consisting of marker chromosomes and of changes in ploidy due to the addition of extra copies of normal chromosomes. Repeat cultures of some lines after one or two years contained most of the markers which had characterized the original samples; additional chromosome abnormalities were also found. An analysis of the break points concerned in the production of markers showed preferential involvement of chromosomes 1 and 5, with a prevalence of centromeric breaks on No. 1. These findings add further weight to the evidence suggesting that changes in chromosome 1 may be of special significance in the pathogenesis of some solid tumours.

Towards a cure of acute granulocytic leukemia

Abstract This paper reviews progress in the therapy of acute granulocytic leukemia (AGL) and examines reasons why its results have remained unsatisfactory. For some years there has been no distinct improvement in remission rates, and survival has not lengthened greatly in most patients attaining remissions. However, in a few patients survival is of considerable length. Improvements in supportive therapy have helped raise remission rates in older patients and in those with high leukocyte counts. Resistance to induction therapy is now mainly due to intrinsic resistance of leukemic cells whose growth kinetics are such that only a minority can respond to cycle-specific therapy. Attempts to manipulate the cell cycle have not so far increased remission rates. No clear evidence exists that maintenance therapy prolongs remissions. Relapses are almost certainly due to re-growth of suppressed leukemic clones. Among new forms of treatment, immunotherapy is not yet securely based. Marrow transplantation may become occasionally useful. It is questionable if cytotoxic therapy alone will improve the prognosis of AGL radically. Though there is little to show that progress towards a cure is being made, new approaches based on a better understanding of the pathology of leukemic growth may eventually be translated into clinical success.

Chromosome studies in fanconi's anaemia before and after treatment with oxymetholone

Summary A 24‐year‐old patient with familial hypoplastic anaemia of the Fanconi type was treated with large doses of oxymetholone. In stimulated cultures of his lymphocytes there were many chromatid and some chromosome aberrations before treatment, but few in cultures taken 5 to 12 months after the beginning of treatment. Little clinical or haematological improvement occurred during this period. Two marrow specimens showed no structural changes, but a minor clone of cells with an aneuploid karyotype was found.

The Value of Chromosome Banding Methods in the Study of Adult Acute Leukaemia

Summary We report on the cytogenetic findings in 46 consecutive patients with acute leukaemia studied by conventional and Giemsa‐banding methods. All except 7 were first studied during the initial or a subsequent relapse. An adequate study was defined as comprising an analysis of 15–30 conventionally stained and of at least 10 banded metaphases, and these criteria were fulfilled in 20 patients. In another 6 patients insufficient banded cells were present, but the cytogenetic status could be established by conventional methods. Among the adequately studied patients in relapse, 46% had abnormal clones, while all patients adequately studied in full remission had only normal diploid cells. Two of the 6 patients studied by conventional methods had abnormal clones. The incidence of abnormal clones in the adequately studied patients in relapse was higher than that previously reported from our laboratory without the employment of banding methods. The most common clonal abnormality was trisomy‐8, confirming the findings of some other authors, and banding methods thus helped materially in demonstrating that, frequently, cytogenetic changes in acute leukaemia are non‐random in origin. However, since adequate chromosome studies were impossible in a substantial proportion of our cases, these methods were of limited value in the investigation of individual patients.

Studies on muramidase in hematologic disorders. I. Serum Muramidase and Serum Lactic Dehydrogenase in Leukemia

Estimations of serum muramidase (S.M.) and lactic acid dehydrogenase (L.D.H.) were made at the time of presentation in 79 adults with various forms of leukemia and compared with a number of other biochemical and hematologic parameters. In 35 patients, serial studies of these enzymes were also carried out. Initial S.M. levels, but not L.D.H. levels, were found to be of assistance in the diagnosis of the type of leukemia present. In patients with acute myeloblastic leukemia (A.M.L.), high pretreatment levels of S.M. tended to have a favorable prognosis. There was good correlation between initial S.M. and L.D.H., serum uric acid, total white cell count, absolute blast and granulocyte counts when all leukemias were taken together. However, this was not a consistent finding in analyses of the individual types of leukemia. In serial studies, S.M., and to a lesser extent L.D.H., paralleled the hematologic fluctuations in a high proportion of cases. When remissions were complete, S.M. and L.D.H. values returned to normal and remained so until relapse supervened. From these studies, we conclude that S.M. and L.D.H. are useful ancillary aids to the methods commonly employed for differentiating the types of leukemia, and that estimations of these enzymes also have some value in assessing the progress and prognosis of the disease.

Contacts among patients with hematological malignancies

A survey was carried out in 2 country areas of New South Wales with the aim of defining contacts among patients with lymphoma, leukemia and myeloma, and of determining whether these were more numerous than among matched controls from the same localities. Cases were identified from records of the N.S.W. Central Cancer Registry and of local doctors and hospitals. 184 cases were found, corresponding to the expected number, and 145 patients, as well as the same number of controls, were interviewed. Of the 290 patients and controls surveyed 111 (38.3%) had had one or more contacts with other patients or controls (37.9% of patients and 38.6% of controls). There were 24 case‐case pairs involving contacts among 33 individual patients, 23 control‐control pairs involving 36 individuals, and 38 case‐control pairs involving 66 individuals. A statistical analysis using a weighting system showed that numbers, closeness and duration of contacts among patients and patients did not differ significantly from those expected. These results thus provide no evidence in favor of the hypothesis that the diseases were transmitted from patient to patient in the survey areas.

Metamorphosis of chronic granulocytic leukaemia arising in an extramedullary site

Abstract A 52 year old man with chronic granulocytic leukaemia, in whom splenectomy had been performed electively early in the disease, developed extramedullary leukaemic deposits in the stomach, in the skin and in lymph nodes. Marked chromosome abnormalities (hyperdiploidy and doubling of the Ph 1 chromosome) were found in a biopsied axillary lymph node at a time when marrow chromosomes showed only a 46XY Ph 1 positive pattern typical of the chronic phase. As metamorphosis of his disease progressed, cells with related chromosome abnormalities appeared in the blood. The sequence of events and cytogenetic changes suggested that cells responsible for metamorphosis appeared first in an extramedullary site and spread from there to the marrow and blood.

Contamination of human melanoma cell lines by mouse L cells

Summary Five of 8 cell lines from human melanomas originally established elsewhere were found to consist exclusively of mouse cells when examined in our laboratory some months after their receipt. Cytogenetic studies, including G‐ and C‐banding, showed that the mouse cells in all cultures had originated from a single cell line, identified as the L‐line. Contamination probably occurred, one year before its discovery, in a laboratory where L cells and human melanoma cells were briefly kept in the same incubator.

Changing clinical, morphological and immunological patterns in chronic lymphocytic leukaemia

Summary Two cases of chronic lymphocytic leukaemia are presented in which, in the terminal phase of the disease, a population of abnormal lymphocytes similar to those seen in lymphosarcoma cell leukaemia replaced the morphologically normal small lymphocytes observed previously. Immunologically, this change coincided with a striking alteration in the pattern of surface immunoglobulin markers. In both cases, most cells initially carried IgM and in both cases these were replaced by cells carrying IgG as the number of abnormal lymphocytes increased. In addition, the use of anti‐5 antiserum in the second case revealed the coexistence of large numbers of IgD‐bearing lymphocytes as well. Calculations showed that more than half the cells present at that time must have been carrying both IgD and IgG surface markers.

Satellite III DNA hybridised to chromosomes from patients with acute leukemia

Abstract Radioactive RNA complementary to normal human satellite III DNA was hybridised to previously Giemsa-banded metaphase chromosomes from six patients with acute leukemia. The distribution of satellite III DNA was found to be the same as in normal subjects, with hybridisation occurring in chromosome 9, the distal arm of the Y and to a lesser extent the centromeric region of chromosome 15. In two leukemic patients hybridisation confirmed that a trisomic or tetrasomic C-group chromosome was 8, as predicted by G-banding, and aneuploidy of chromosome 9 was not seen in any one case.