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PubMed1985

CFU-gm assay, cytochemical and electron microscopic studies in agar in patients with preleukemic syndrome and aplastic anemia.

Thirty-seven patients with chronic cytopenia were studied using a CFU-gm assay in agar. Cell proliferation was evaluated on days 2, 3, 5, 7, and 10 of incubation. Growth patterns were different in cultures of hematologically healthy persons versus patients with preleukemic syndrome (PL) and aplastic anemia (AA). Three types of PL syndrome and two types of AA (C1 and C2) were distinguished. Bone marrow dysfunction was evaluated further using cytochemistry and electron microscopy to morphologically study cell proliferation in vitro. Cytochemical staining performed in agar demonstrated well-defined maturation defects in myelopoietic precursor cells from the bone marrow of PL patients. Electron microscopic findings of Auer-body-like inclusions in "statu nascendi" in the vacuoles of preleukemic cells supported our results. PL patient groups at high risk for development of overt leukemia and patients with grave prognosis in AA were distinguished. Our results are relevant for the clinical diagnosis and prognosis of patients with cytopenia.

Aged↗
PubMed2001

Evolving concepts in myelodysplastic syndromes.

Myelodysplastic syndromes continue to be "a riddle, wrapped in a mystery inside of an enigma". Clearly, MDS represent a heterogeneous group of disorders, and no uniform etiology or treatment can be prescribed for all patients. This further underscores the need for MDS patients to be seen at specialized centers and placed on experimental protocols if they need treatment. The important thing to remember is that ultimately, the patient must remain the measure of all things, and must be given all the therapeutic choices including that of waiting and watching with supportive care alone. Recent biologic insights have expanded the therapeutic options, but no curative therapies except stem cell transplants are available at this time. By dissecting the biology and focusing efforts towards understanding the etiology of the cytopenias, significant therapeutic advances are being made in this disease. The momentum built up so far must not be lost now.

Aged↗
PubMed2001

Molecular, cytogenetic and genetic abnormalities in MDS and secondary AML.

Myelodysplasia (MDS) is a clonal disease, which increases with age, suggesting that multiple steps are required for the evolution of the condition. Approximately 30% of MDS evolve into acute myelogenous leukemia (AML). In this review, we intend to delineate the genetic events, which may drive this sequence and therefore we will focus primarily on cytogenetic abnormalities where the genes have been identified and oncogenes and suppressor genes that have been implicated. In terms of the biological mechanisms, which characterise this process, it is generally thought that the MDS cell has impaired differentiation, and has increased apoptosis. As the disease progresses in addition, the cells have increased proliferation. As the disease evolves, the population of cells, which predominate remain immature, have decreased apoptosis and in many cases, upregulate anti-apoptotic genes and have deregulated proliferation as the number of blast cells increase. Etiological factors, which contribute to the development of leukemia, include therapeutic agents administered for a primary malignancy. The cytogenetic abnormalities, predisposition factors and genes involved in secondary leukemia will also be reviewed.

Acute Disease↗
PubMed1979

Serum and secretory immunoglobulin levels in preleukaemic AKR mice and three other mouse strains.

Levels of IgM, IgC1, IgG2 AND IgA were determined in serum and milk of AKR mice, which spontaneously develop lymphoma at 6--14 months of age. As a reference C3H, CBA and C57BL mice were studied. Of the four mouse strains studied AKR had the lowest serum and secretory IgA levels. The values of the other immunoglobulins in AKR mice were comparable to those of CBA mice. C3H and C57BL mice had significantly higher immunoglobulin levels. Serum of lactating mice showed fairly decreased IgG1 and IgG2 levels as compared with non-lactating mice, probably due to transudation into the milk. The serum IgM and IgA levels were not consistently affected by lactation.

Allergy and Immunology↗
PubMed1976

Blood groups changes in preleukemic states.

Modifications of blood groups in the course of malignant hemopathies are related to the disease itself and appear to be essentially clonal. They refer not only to the glycolipidic ABH and associated antigens, but also to other blood group systems or other genetic markers. These multiple abnormalities are observed in the preleukemic states as well as in the actual leukaemias. Similar but limited to one genetic unit abnormalities have been noticed among apparently normal subjects, especially in the aged. The various modifications observed are indeed related to the genetic function, and the clonal character is in favor of this assumption. The evidence of abnormalities affecting two genetic systems which are linked ABO and AK is a further argument supporting this hypothesis. Furthermore, the distribution of immunoglobulin marker abnormalities corresponds to that of one of the haplotypes of the Gm genotype. Finally, we were able to demonstrate that the glycosyltransferase itself is abnormal too, in the case of ABH antigen abnormalities. In all the cases investigated to date, when apparently new characters seemed to be observed, they are in fact unconverted substrates, which are to be compared to the carcinoembryonic antigens.

ABO Blood-Group System↗
PubMed1976

Cell membrane antigens associated with human adult acute leukemia.

Cell membrane antigens associated with the blast phase of human acute leukemia are separable from inhibitory proteins and from histocompatibility antigens also present in the membranes. Since these antigens are not detectable in remission or normal white blood cells, they provide a useful marker for identification of cells undergoing carcinomatous changes. Blast antigens from acute lymphatic leukemia (ALL) are also present on early human fetal thymus cells; antigens from both sources produce cell-mediated immune (CMI) responses and are structurally similar. Blast antigens from acute myelocytic leukemia (AML) are not associated with fetal antigens and do not cross react with ALL antigens. ALL cells possess a larger quantity of CMI inhibitory protein than AML cells. The isolation, purification and idenfication of these blast antigens is a step toward their use in studying cultured and cloned subpopulations of cells thought to be associated with pre-leukemia.

Antigens↗
PubMed1976

The preleukemic syndrome: clinical and laboratory features, natural course, and management.

The clinical and laboratory features of the stages in the evolution of acute nonlymphocytic leukemia are reviewed. Based on a retrospective analysis of 34 patients who died with an acute myelomonoblastic leukemia, the "preleukemic syndrome" has been shown to display a clinical picture sufficiently specific to permit its recognition prospectively (i.e., before the development of overt leukemia). The results to date of a variety of prospective studies are reviewed, and the approach(es) to the management of these cases is considered.

Adrenal Cortex Hormones↗
PubMed1976

Preleukemic states in atomic bomb survivors in Japan.

Cytologic and cytogenetic studies were performed on the bone marrow cells in atomic bomb-exposed patients who had prolonged periods of blood disorders with termination of acute leukemia (group I, 6 cases) and without the termination (group II, 6 cases), and survivors who were in apparent good health (group III, 85 cases). All but one patient in group I, who were examined at the preleukemic state, had abnormal clones. In 4 out of 6 of group I patients, morphologic abnormalities of bone marrow cells taken 3-10 years before leukemic development were found, such as giant neutrophils or basophils, binucleated granulocytes or megakaryocytes, and bridge formation of chromatid in metaphases. All patients in group II had stable types of chromosome aberrations. The types of cytologic abnormalities were similar to those in group I, but the frequencies were a little less than those in group I. In group III, 14 persons were found to have stable types of chromosome aberrations, of which 11 persons had apparent but transient clone formations. Cytologic and clinical abnormalities were not observed in the group. The persistent and high percentages of cytologic and cytogenetic abnormalities in patients with prolonged periods of blood disorders, regardless of history of radiation exposure, would suggest a preleukemic state, and also give some clue to the problems of leukemogenesis.

Acute Disease↗
PubMed1976

Acute myeloblastic leukemia after immunodepressive therapy for primary nonmalignant disease.

Three patients treated with immunodepressive chemotherapy over a period of 43, 60, 38 months respectively, for primary nonmalignant disease, developed AML after cessation of chemotherapy. During the months preceding the AML outbreak, there were hematologic changes with seemed to reveal a preleukemic state. Our 3 patients, and 8 previously published cases, making a total of 11 patients, developed AML after chemical immunodepression for reasons which were neither hematologic nor neoplastic.

Arthritis, Rheumatoid↗
PubMed1976

Prediction of relapse and remission in AML by marrow culture criteria.

Bone marrow culture studies in semi-solid agar have been performed on 250 patients presenting with acute myeloid leukemia. The detection of a spectrum of qualitative defects in the proliferation, differentiation and biophysical characteristics of leukemic colony forming cells (CFU-c) has permitted a detailed analysis of the relapse-remission status based on transition from qualitatively abnormal cell growth in vitro to a normal pattern of proliferation and differentiation. Changes in vitro generally preceded clinical or morphological evidence of the onset of relapse or remission and serve as a valuable additional parameter in monitoring clinical status. Marked cyclic changes in CFU-c incidence appeared to characterize the remission phase of AML and were frequently associated with fluctuations in marrow blast cell count which can lead to mis-diagnosis of incipient relapse. Detection of qualitative defect in marrow culture serves to distinguish patients with preleukemic disorders at high risk of termination in acute myeloid leukemia from patients with clinically similar disease who have not undergone further progression over a 2-4 year period of observation.

Bone Marrow↗