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PubMedDate not supplied

Aplastic anemia or aplastic preleukemic syndrome?

The incidence of aplastic anemia appears to be relatively high in some parts of the world, including Pakistan. Since some of the etiological factors are shared by aplastic anemia and the preleukemic syndrome, there is a strong possibility that a proportion of cases of aplastic anemia may in fact be preleukemia. The study of chromosomes offers a relatively easy method of detecting cases of preleukemia, because some chromosomal abnormalities are frequently observed in this condition. Chromosomal studies were carried out in peripheral blood cell cultures of 31 patients with otherwise typical aplastic anemia. Chromosomal abnormalities were detected in 7 (22.5%) cases. The most common chromosomal abnormality detected was trisomy 8, seen in four cases. Other abnormalities detected were 22q-, t(14;22) and t(15;21), in one case each. These abnormalities have been found to be associated with AML, MDS, ALL, and NHL as well. We hypothesize that a proportion of cases of otherwise typical aplastic anemia may in fact be due to a leukemic process in evolution.

Adolescent↗
PubMed1991

Relationship between clonality and transformation in acute leukemia.

In some cases of acute leukemia an initial potentially leukemogenic genetic alteration can result in clonally derived end-cells normal in appearance and numbers. We refer to this clonal expansion as preleukemia. Subsequent alterations, intrinsic or extrinsic, often referred to as transformation, result in abnormal differentiation and/or growth regulation; we refer to this as leukemia. Several issues are unresolved. Where in the hierarchy of hematopoiesis clonal expansion and transformation occur is unknown. It is quite likely that clonal expansion occurs in cells with considerable self-renewal potential--probably stem or progenitor cells. The precise site may vary in different cases and account for the diverse phenotypes of acute leukemia. How the preleukemia clone comes to dominate hematopoiesis and the fate of the residual normal stem cells and their progeny are also unknown. Likewise, there is controversy whether different models of leukemogenesis operate in different subjects. For example, are older persons or those with occupational exposure to potentially leukomogenic agents more likely to exhibit one pattern of leukomogenesis? Finally, it is unknown whether these diverse models of leukemogenesis respond differently to therapy.

Acute Disease↗
PubMed1975

Proliferation and maturation of human leukemia cells in liquid culture.

Bone marrow from patients with acute myelogenous leukemia (AML), acute myelomonocytic leukemia (AMML), chronic myelogenous leukemia (CML), preleukemia, and from healthy volunteers was cultured using a recently developed liquid diffusion technique. Differential and viable cell counts and 3H-thymidine labeling indices were performed at intervals up to 30 days. Differentiation was assessed morphologically by light and electron microscopy, histochemically, and by functional tests for phagocytosis and the presence of surface receptors for IgG. Colony-stimulating activity (CSA) was assayed against normal human bone marrow by the agar colony technique. In acute leukemia cultures, viable cell counts usually fell within the normal range. However, most AML cells failed to demonstrate significant maturation in vitro, and did not produce detectable CSA. In AMML cultures, maturation was defective but some differentiated macrophages were observed and the cells produced high concentrations of CSA. Preleukemic cultures demonstrated normal growth but maturation was impaired as evidenced by a high percentage of immature cells during the first 7 days. CML cultures showed abnormally high growth capacity resulting in viable cell counts 2-3 times normal. In the chronic phase of CML, maturation was qualitatively normal and the cells produced CSA. With the onset of blast transformation, maturation became abnormal but growth remained high. These studies support a concept of AML as a primary defect in cellular maturation and of CML as a primary abnormality of proliferation. The production of CSA by neoplastic cells relates to the degree of monocyte-macrophage differentiation within the leukemic population. Human preleukemia is characterized by a failure of normal maturation in vitro.

Bone Marrow↗
PubMed1990

[Comparison of HIV-associated dyshemopoiesis in myelodysplastic HIV-negative patients].

Bone marrow biopsies of 23 HIV-1 infected patients and 29 patients with myelodysplastic disorders were examined histologically by immuno- and enzyme-histochemical techniques and morphometrical methods. The nucleolar organizer regions (AgNOR) were demonstrated and visually counted. Hypercellularity in marrows of AIDS patients is substantially caused by an increase of erythropoiesis and CD68+ macrophages/reticular cells. However, hypercellularity in preleukemia results from hyperplasia of all hematological cell lines and CD68+ bone marrow macrophages/reticular cells. AgNOR count is positively correlated with granulo- and erythropoiesis in preleukemia. In AIDS there is such a positive correlation between AgNOR count and granulopoiesis whereas an inverse relationship appears in erythropoiesis. The results suggest that HIV-associated bone marrow alterations differ from merely reactive changes and are related to myelodysplastic disorders.

Acquired Immunodeficiency Syndrome↗
PubMed1991

[Stem cells, clonality and leukemia].

The data we review suggest newer concepts regarding the biology of leukemia. First, all leukemias may originate in a multipotent stem cells. Second, leukemia phenotype may reflect where the leukemia clone expands rather than the site of transformation. Third, preleukemia may always antedate leukemia. And finally, remission and cure may result from re-establishing preleukemia rather than eradicating leukemia cells of favoring their maturation. Also, leukemia and at least some cases of aplastic anemia may represent different ends of a spectrum of one disease.

Clone Cells↗
PubMed1987

Refractory anemia in the elderly.

Anatomical observations have indicated a decrease of marrow cellularity with age, but these changes are not associated with anemia in the healthy geriatric patient. Aged patients with refractory anemia should be studied by utilizing red cell volume (MCV) and red cell heterogeneity (RDW). A classification with these indices initially can separate the anemias for a more fruitful investigation. By old age the anemias of hereditary red cell membrane or hemoglobin disorders should be known to the patient. In the absence of tumor, elderly patients have an increasing frequency of refractory anemias that can be called preleukemia or myelodysplastic syndrome. Morphological observations have emphasized the importance of abnormal megakaryocytes and platelets in all phases of preleukemia, and these cytologic changes should be used to guide the physician in the early diagnosis of the syndrome complex. This group of refractory anemias have a limited survival, but nonspecific marrow stimulation can be effective and should be tried. With a more complete classification of the chromosomal abnormalities in the myelodysplastic syndrome, a more accurate prognosis can be anticipated. The anemias of marrow aplasia and ineffective iron utilization (anemia of chronic disease) are found frequently in the elderly, and the physician may offer more effective therapy by an early diagnosis.

Aged↗
PubMed1985

The clinical significance of cytogenetic studies in 100 patients with multiple myeloma, plasma cell leukemia, or amyloidosis.

Chromosome studies were done on 82 patients with multiple myeloma, 11 with amyloidosis, 2 with multiple myeloma and amyloidosis, and 5 with plasma cell leukemia to investigate their chromosomal abnormalities and to determine the usefulness of cytogenetic studies. A chromosomally abnormal clone was found in 29 patients but was observed most often in those with active disease: in 18% of patients with newly diagnosed multiple myeloma, in 63% with aggressive disease, and in 40% with plasma cell leukemia. Survival among the newly diagnosed patients was significantly shorter (P = .0089) for those in whom an abnormal clone was identified (median survival, six months) than for those in whom only normal metaphases were observed (median survival, greater than 12 months). Among all of the patients, survival from the time of chromosome analysis was shorter for those in whom a chromosomally abnormal clone was found: the median survival was three months for patients with all abnormal metaphases and eight months for patients with normal and abnormal metaphases and has not yet been reached for patients with only normal metaphases. The most common anomalous chromosomes in patients with a plasma cell proliferative disorder were 1, 11, and 14: 11 patients had an abnormality involving chromosome 14q32 and nine patients had an anomalous chromosome 11. The single most common abnormality, a t(11;14)(q13;q32), occurred in three patients. Among the patients who developed preleukemia or acute nonlymphocytic leukemia, the most common anomaly involved chromosome 7. The results suggest that cytogenetic studies are useful for identifying patients who have a poor prognosis and can help distinguish patients with a cytopenia because of preleukemia from those with an aggressive plasma cell proliferative process.

Amyloidosis↗
PubMed1984

Evaluation of role of natural killer cells in radiation-induced leukemogenesis in mice.

The relationship of the leukemogenic and natural killer (NK)-suppressive effects of fractionated doses of gamma-radiation in mice was studied. A/J mice were relatively resistant; CBA/J, BALB/c, and C57BL/6 were susceptible to both the NK-suppressive and leukemogenic effects, and young (1 mo old) C57BL/6 mice were more susceptible than were 2- and 3-month-old C57BL/6 mice to both effects. Age-dependent susceptibility to radiation-induced leukemogenesis also was observed in C57BL/6 (bg/bg) (beige) mice. No differences in incidence and latent period of lymphoma development were found between C57BL/6 (+/+) and beige mice. Bone marrow cells (BMC) from normal C57BL/6 donors reconstituted the NK reactivity of irradiated C57BL/6 (+/+) or beige recipients and inhibited leukemogenesis. Although BMC of beige donors did not reconstitute the NK reactivity of irradiated C57BL/6 (+/+) or beige recipients, these cells were as efficient for antileukemic protection as were BMC from C57BL/6 (+/+) mice. The bone marrow of irradiated mice contained preleukemia cells that produced leukemias when transplanted iv into recipients preirradiated with 400 R. Inoculation (iv) of spleen cells (SpC) from syngeneic nude mice plus preleukemia bone marrow cells (PBMC) were able to inhibit leukemia formation in the 400 R-irradiated recipients. SpC from beige mice, normal C57BL/6 (+/+) mice, or C57BL/6 (+/+) mice treated with anti-asialo GM1 serum had no influence on the development of leukemia after their transplantation with PBMC.

Aging↗
PubMed1978

Chromosome studies in preleukemic states. IV. Myeloproliferative versus cytopenic disorders.

The prognostic value of marrow chromosome studies was examined in 112 "preleukemic" patients followed for at least one year or until death. Based on recent definitions, 49 patients were classified as myeloproliferative disorders (MPD) (polycythemia vera, myelofibrosis, undifferentiated myeloproliferative disorder, essential thrombocythemia), and 58 as cytopenic states (refractory anemia, pancytopenia). In each group, approximately one-third had a chromosomally-abnormal clone. For MPD, this had little predictive value, but in the cytopenias, 77% with a cytogenetic abnormality developed leukemia versus 39% without. Twelve cytopenic patients had multiple alterations involving more than 2 chromosomes and 11 died within 6 months, 9 with leukemia. Such patients may warrant consideration for aggressive chemotherapy before the appearance of clinical leukemia. Banding studies did not reveal any specific chromosome abnormalities consistently associated with these various preleukemic disorders, or with progression to leukemia, but nonrandom alterations were noted involving chromosomes 1, 5, 7-9, and 20 in the MPD group, and chromosomes 6 and 16 in the cytopenic patients. Correlation of these data with other reports indicates that certain cytogenetic abnormalities involving specific segments of the human genome confer a selective growth advantage on hemic clones which may present clinically as either preleukemia or leukemia.

Adult↗
PubMed1979

Erythroleukemia in a renal transplant recipient.

A 53-year-old male developed acute erythroleukemia three years after renal transplantation. He had received three years of immunosuppressive therapy with azathioprine. A preleukemia phase associated with chromosome abnormalities was recognized. Azathioprine has been associated with chromosome abnormalities. The chronic stimulation of an abnormal erythroid clone by transplantation may have hastened the development of erythroleukemia.

Azathioprine↗
PubMed1986

Chromosome studies in preleukemic states. V. Prognostic significance of single versus multiple abnormalities.

The prognostic value of marrow chromosome findings was examined in 242 patients with preleukemic myelodysplastic syndromes (MDS) or myeloproliferative disorders (MPD), with emphasis on the significance of single versus multiple karyotypic changes. In both groups, the results showed that patients with multiple chromosome abnormalities in a marrow clone had a very high probability of early death, from progression to leukemia or from other complications of hematopoietic dysfunction. Conversely, in patients with a hemic clone having only one karyotypic alteration (involving a single chromosome or single translocation), survival over 2 years was only slightly reduced as compared to those without chromosome abnormality. The only single karyotypic alteration perhaps associated with a markedly shortened survival was monosomy 7. These findings suggest that the conclusions of previous studies concerning the grave consequences of chromosome alterations in preleukemia largely reflect the clinical significance of clones with multiple cytogenetic changes. Prior knowledge of the karyotypic status of preleukemic patients should be helpful in evaluating current attempts to find effective treatment for these difficult disorders.

Aged↗
PubMed1989

Development of leukemia after doxorubicin and cisplatin treatment for ovarian cancer.

Alkylating agents have been the major group of chemotherapeutic agents associated with an increased incidence of secondary leukemias. In ovarian cancer alkylating agents have resulted in a lesser, although still increased, risk of secondary malignancies. This paper reports two cases of ovarian cancer treated with cisplatin and doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH), and the subsequent development of an acute nonlymphocytic leukemia and a preleukemia syndrome. This regimen does not contain alkylating agents, and has not been associated with leukemia in patients with ovarian cancer. In these two cases, abnormalities of chromosomes 5, 7, 11, and 17 are reported which have been shown to occur in therapy-related leukemia.

Adenocarcinoma↗
PubMed1988

Pure red cell aplasia as possible early manifestation of chronic myeloid leukemia.

Cytogenetic studies as well as erythroid and myeloid progenitor cell assays were performed in a 29-yr-old epileptic man with pure red cell aplasia (PRCA) who had been treated with primidone for several years. Despite clinical evidence of preleukemia, our studies indicated an underlying atypical Philadelphia chromosome-positive myeloproliferative disorder. These laboratory findings were confirmed by the subsequent development of chronic myeloid leukemia (CML) which terminated in a CALLA-positive lymphoblastic crisis 32 months later. The rare concurrent occurrence of PRCA and CML and the possible inducing role of the preceding antiepileptic treatment are discussed.

Adult↗
PubMed1980

General report on the Second International Workshop on Chromosomes in Leukemia.

The workshop participants were able to establish that the t(8;21) and t(15;17) are each definitely associated with a particular type of ANLL, namely, AML-M2 and APL-M3 and M3 variant, respectively. Both translocations, particularly the t(15;17), have an uneven geographical distribution which cannot presently be explained. The data also show that patients with preleukemia and an abnormal karyotype have a very poor prognosis with a fatal outcome in 60%, compared with only 30% for patients with a normal karyotype.

Chromosome Aberrations↗
PubMed1976

The cellular distribution of erythrocyte and normoblast A1 and A antigens in normal and preleukemic states. An immunoelectron microscopy study.

A1 and A alloantigens were visualized on human erythrocytes and normoblasts by immunoelectron microscopy using peroxidase-coupled antibodies. Specimens were obtained from patients with preleukemia and associated antigen weakening, and from individuals with normal antigen values. Cells were fixed by glutaraldehyde and subsequently reacted with antibodies.

ABO Blood-Group System↗
PubMed1980

Chromosomal studies of leukemic and preleukemic Fanconii's anemia patients: examples of acquired 'chromosomal amplification.'.

Cytogenetic studies of three Fanconi's anemia patients are reported, one of the patients having erythroleukemia, the other two preleukemia. Clonal abnormalities were present in all three cases. Partial chromosomal duplication uncommon in other leukemias was observed. Partial duplication of the long arm of chromosome 3 has been observed in the present case of erythroleukemia examined as well as in a previously reported one.

Adolescent↗
PubMed1978

Conversion of polycythemia vera to refractory anemia with hyperplastic bone marrow.

Clinical and morphologic findings in the conversion of treated polycythemia vera to pancytopenia with hyperplastic bone marrow (refractory anemia or pancytopenia with hyperplastic bone marrow) are described in light of our own observation. The nomenclature associated with this condition (pancytopenia, chronic erythroleukemia, preleukemia) is not uniform, whereas the morphologic findings are virtually identical. Some patients subsequently develop acute leukemia. The prognosis in cases of refractory anemia with hyperplastic bone marrow following polycythemia vera is, independent of the subsequent acute leukemia, invariably terminal.

Anemia, Aplastic↗