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PubMed1989

[Relation of karyotypic findings to chemotherapy response in patients with preleukemia].

In 1982, the French-American-British (FAB) Cooperative Group proposed the myelodysplastic syndrome (MDS), which comprised a group of heterogeneous hematologic disorders characterized by various degrees of cytopenias and a possibility of leukemic transformation. And chromosome findings of bone marrow cells from patients with this syndrome are reported to have one of the greatest prognostic significance. In our chromosome study of 97 patients with MDS, we found clonally abnormal karyotypes in 61 patients (63%), including the whole chromosome or partial loss of long arm of chromosome 7 (-7/7q-) in 18 patients and a partial loss of chromosome 5 (5q-) in 14 patients. Among these 97 patients, 26 received cytostatic chemotherapy (small dose of cytarabine; 23 patients, small dose of behenoyl Ara-C; 2, and intensive combined chemotherapy; 1) as well as supportive care. Among these 26 treated cases, pretreatment hematological characteristics or FAB subclassifications were not associated with response to chemotherapy. In contrast, only one of 9 patients with -7/7q- and/or 5q- achieved a partial remission, while 5 of 8 patients with other abnormal karyotypes and 4 of 9 patients with normal karyotype achieved a complete (4 patients) or a partial remission. In conclusion, pretreatment cytogenetic findings can predict the potential responders to this chemotherapy, and may be one of the most important factors in the selection of the treatment for this ill-managed syndrome.

Adult↗
PubMed1986

Analysis of leukocyte differentiation antigens in blood and bone marrow from preleukemia (refractory anemia) patients using monoclonal antibodies.

Peripheral blood and bone marrow mononuclear cells from patients with refractory anemia (RA) or RA with sideroblasts (defined according to the revised French-American-British classification with less than 5% blast cells in the bone marrow) were analyzed using a panel of monoclonal antibodies directed against leukocyte antigens on B lymphocytes, T lymphocytes, monocytes, and myeloid cells. In the peripheral blood an increased proportion of T lymphocytes (and correspondingly a decreased proportion of B cells) could be demonstrated. However, when expressed in terms of absolute numbers, the T cell component was depressed because of severely decreased numbers of T4+ helper cells. In contrast, the absolute numbers of T8+ suppressor cells were either normal or increased in the majority of the patients. This resulted in markedly decreased ratios of T4+/T8+ cells, which were closely correlated to the number of transfusions given to the patients because of their refractory anemia. Finally, nearly all of the patients exhibited decreased numbers of cells reactive with the N901 natural killer (NK) antibody, thus explaining our earlier finding of decreased NK activity in these patients. In the bone marrow increased proportions of myeloid cells reactive with monoclonal antibodies present on immature myeloid cells (My7 and My9) were found, suggesting the presence of malignant clones. Indeed, when the numbers of My7+ cells and the morphologic evaluations of bone marrow smears at the time of diagnosis were compared to the progression of the disease, a group of patients with high numbers of My7+ cells and normal morphology could be identified that had a high probability of progression to refractory anemia with an excess of blasts or to overt acute myeloid leukemia. Thus, the use of antibodies defining leukocyte differentiation antigens might be of significant value in the diagnosis and prognostication of the myelodysplastic syndromes. These findings are discussed in relation to the pathogenesis of this potentially premalignant condition with special emphasis on possible defects in the immunologic defense mechanisms against early neoplasias.

Anemia, Refractory↗
PubMed1988

Successful transplantation of Friend virus-induced preleukemia into stem cell-deficient fetal mice.

The leukemias induced by the Friend polycythemia virus and other leukemogenic retroviruses have previously not been transplantable until weeks or months after virus inoculation. Because tumor-specific immune mechanisms persist in both irradiated and nude mice, it has not been possible to determine if this result is due to rejection of cells already immortalized by retrovirus infection, or reflects an inherent limitation in the proliferative capacity and malignancy of these "preleukemic" cells. To clarify these issues, we have transplanted virus-infected bone marrow into mouse fetuses that are immunologically immature and thus incapable of graft rejection. We report here that within days of virus inoculation, transplantable cells capable of disease progression in certain fetal hosts can be detected with this technique. These results demonstrate that cells with the capacity for extensive leukemic proliferation arise very early in Friend virus-induced disease. However, successful transplantation was seen only in genetically anemic recipients (Wx/Wv), which are deficient in hematopoietic stem cells, and not in their normal littermates. Thus, in accord with recent in vitro observations, this in vivo data suggests that normal hematopoietic cells, independent of immune mechanisms, can suppress the malignant progression of transformed cells.

Animals↗
PubMed1987

Preleukemia in Fanconi's anemia: hematopoietic cell multinuclearity, membrane duplication, and dysgranulogenesis.

A 25-year-old male had Fanconi's anemia characterized by small stature, the onset of pancytopenia in the first decade of life, a high spontaneous breakage rate of the chromosomes, and the development of acute myeloblastic leukemia. In the preleukemic phase, marrow erythroblasts were multinucleated, and had duplicated nuclear and cytoplasmic membranes with frequent nuclear pockets and cytoplasmic vacuoles, respectively. All neutrophilic and eosinophilic granulocytes had severe quantitative and qualitative defects of granulogenesis; autophagy and nuclear pockets were also observed in the majority of granulocytic cells. Platelets had decreased granulation and extremely dilated canaliculi. Decreased titration scores with anti-I and anti-i were observed with the patient's erythrocytes and those of his clinically normal mother. The unusual morphologic and serologic findings in this patient appear to have resulted from a membrane abnormality affecting the cells of several hematopoietic lines and their organelles.

Adult↗