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PubMed1981

A case of progressive multifocal leukoencephalopathy in preleukemic syndrome.

A case of an apparently primary PML in a 57-ys-old female is reported. The first neurological symptoms appeared about one year before death. The hematological abnormalities observed only during the last two months of life, at postmortem examination, were found to fit the criteria of the preleukemic syndromes.

Brain↗
PubMed1976

Surface features of cells in human lymphoproliferative disorders. An immunoelectron microscopy study.

Peroxidase conjugated antibodies were applied to cell suspensions in order to detect surface associated immunoglobulins. Cell suspensions were fixed prior to incubation with reagents, a procedure avoiding membrane alterations induced by antibodies to surface component. By immunoelectron microscopy an identification of B lymphocytes could be made with simultaneous observation of their surface architecture. Basic findings were that normal circulating human B lymphocytes had a villous surface. This relationship was not confirmed however by examinating samples from various B and T cell proliferations establishing that surface morphology is not sufficient to categorize cells in disease. Specimens from hairy cell leukemia were also examined. Despite salient surface characteristics as revealed by the present method, the categorization of cells remains unclear.

B-Lymphocytes↗
PubMed1976

Clinical utility of bone marrow culture.

Standardized culture of bone marrow in soft agar permits the detection of a population of granulocyte-macrophage progenitor cells (CFU-c). A spectrum of qualitative abnormalities serves to distinguish myeloid leukemic CFU-c from normal and remission populations. These abnormalities in maturation and proliferation are diagnostic of a myeloid leukemic state and serve to functionally reclassify acute myeloid leukemia at diagnosis into a number of categories based on in vitro growth pattern. The virtue of this classification is that it permits detection of a substantial number of patients who are refractory to conventional remission induction protocols. The clear distinction between normal and leukemic growth in vitro permits early detection of emerging remission CFU-c during induction therapy and of early onset of relapse in patients who are otherwise in complete remission. In patients with leukemia undergoing allogeneic bone marrow engraftment, marrow culture has proved of value in documenting the reconstitution of the patient and in detecting re-emergence of the original leukemic stem line prior to its detection by cytogenetic and hematological techniques. Serial studies on patients with chronic myeloid leukemia have allowed early diagnosis of blastic transformation and classification of blastic phase disease on the basis of in vitro growth pattern has revealed a similar spectrum of in vitro abnormalities as seen in AML. The cloning of normal or leukemic human myeloid progenitor cells (CFU-c) in agar or methylcellulose has permitted analysis of both quantitative and qualitative changes in this cell compartment in leukemia and other myelodysplastic states (1-7). Among these changes are abnormalities in maturation of leukemic cells in vitro (4, 5, 6), defective proliferation as measured by colony size or cluster to colony ratio (5, 6), abnormalities in biophysical characteristics of leukemic CFU-c (4, 5), regulatory defects in responsiveness to positive and negative feedback control mechanisms (8, 9) and the existence of cytogenetic abnormalities in vitro (10, 11). Detection of this spectrum of abnormalities has proved of clinical utility in diagnosis of leukemia and preleukemic states (5, 6, 12), in classification of leukemias and myeloproliferative diseases (5, 6), in predicting remission prognosis and response to therapy (5, 13), in predicting onset of remission or relapse in AML (13) and in monitoring the progression of chronic myeloid leukemia or preleukemic disease (4, 14). The present communication serves to illustrate the clinical applications of bone marrow culture in these various areas.

Blood Cells↗
PubMed1983

Karyotypic progression in human tumors.

Karyotypic progression may be viewed in at least two ways. One approach seeks evidence for increasing and progressive deviation from the normal chromosome pattern in tumors. The clearest examples, found in some leukemias, are those in which successive karyotypic changes are superimposed on an already aberrant cell population. Evidence of chromosomal progression within solid tumors is far less frequent, possibly because the tumors themselves are at a relatively late stage in their evolution. An alternative approach, therefore, attempts to correlate the extent of karyotypic deviation with other aspects of tumor progression. Recent data, based on classical cytogenetic analyses and flow cytometry, are presented to determine relationships between karyotype and specific origin and morphology of tumors. The predominant theme which emerges, not surprisingly, is that the more deviant chromosome patterns are associated with other measures of increased biologic malignancy. What is surprising is the degree to which these properties are expressed in primary tumors and the relative lack of evidence for further karyotypic evolution with recurrence or metastasis. Examples of genetic instability, evolution through polyploidy, gene amplification, and selection for specific chromosomal rearrangement are found in populations of premalignant and malignant human cells. There is increasing recognition of the importance of tumor-specific chromosome aberrations in the stepwise progression from the normal to the fully neoplastic cell.

Chromosome Aberrations↗
PubMed1980

Cold synchronization for the study of peripheral blood and bone marrow chromosomes in leukemias and other hematologic disease states.

A method of cold-shock synchronization of immature granulocytic cells from peripheral blood or bone marrow is described. It is shown that this method provides an increased yield of early metaphases and offers advantages over others currently employed. The peaks of mitotic activity following the cold-shock treatment differ for patients with acute nonlymphoblastic leukemia (ANLL) and patients with chronic myeloid leukemia (CML) by an interval of 2 h. This method is considered to be suitable for routine cytogenetic studies on hematological patients.

Acute Disease↗
PubMed1986

Chromosome changes in human monocytic cell lines with in vitro spontaneous malignant transformation.

Serial chromosome studies were performed on four monocytic cell lines established from bone marrow samples of patients suffering from hematopoietic disorders other than leukemia. A spontaneous in vitro transformation towards a malignant phenotype has been found to be related to the karyotype evolution. The correlation between the chromosome changes of these cell lines and those described in human cancer and leukemia is discussed.

Adolescent↗
PubMed1982

Pathogenetic significance of "pure" monosomy 7 in myeloproliferative disorders. Analysis of 14 cases.

Monosomy 7 is frequent in acute myeloid leukaemia (AML) and in preleukaemic dysmyelopoietic syndromes but often it is not the only chromosome anomaly associated with these conditions. We report 14 patients with "pure" monosomy 7 and their clinical and haematological data are analysed in order to clarify the possible implications of this chromosome anomaly. The following points are considered: 1) In spite of the apparent variability of clinical forms in which monosomy 7 is found, several characteristics are common to all monosomy 7 patients, i.e. the presence of a preleukaemic phase and blood and marrow features suggesting the early involvement in the disease of all marrow cell lines. The different diagnoses associated with monosomy 7 are correlated with different steps of a unique myeloproliferative disease whose typical course can be reconstructed. 2) Monosomy 7 has a negative prognostic value. When it is found in a preleukaemic disorder it indicates a high risk of progression to AML, while in AML it implies recurrent infections, poor response to therapy and short survival. 3) The significance of the lack of Colton blood group antigens in monosomy 7 patients is discussed, with particular regard to the fact that the patients in whom this lack was found are the only ones who had not received transfusions in the months before the tests were done. 4) The finding of defective neutrophil chemotaxis in monosomy 7 patients is confirmed and the clinical importance of this fact is emphasized. 5) The data on the 14 patients support the opinion that AML, in general, is heterogeneous in origin. It is postulated that monosomy 7 is a marker of a specific pathogenetic pathway of AML, which implies the beginning of the malignancy in a pluripotent stem cell.

Adult↗
PubMed1984

Treatment of therapy-induced preleukemic syndrome.

Two young adult patients with therapy-induced preleukemic syndrome and Hodgkin's disease as primary malignancy were treated with aggressive antileukemic regimens before the establishment of leukemic conversion. Pretreatment clinical staging procedures did not reveal recurrence of Hodgkin's disease. One of the regimens consisted of an HLA-identical allogeneic bone marrow transplant and the other of high dose cytosine arabinoside. Both therapeutic approaches have proved successful in restoring normal hematopoiesis with reversal to normal karyotypes and unmaintained remissions 556 and 192 days post-treatment. The rationale for such a therapeutic approach in the preleukemic stage of therapy-induced leukemogenesis is discussed.

Adult↗