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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the past, studies on CD34+ cells have been based on the use of monoclonal antibodies conjugated with different fluorochromes that show different fluorescence intensity and yield variable results. Moreover, most of these studies have neither specifically focused on adult human BM samples nor have they used combinations to explore specifically the phenotype of myeloid committed CD34+ cells. The aim of the present study has been to characterize the normal human CD34+ precursor cells from adult BM in order to identify missing or extremely rare phenotypes that can be used for detecting minimal residual disease (MRD) in patients with AML. For this purpose we have utilized the fluorochrome conjugates that provide the most sensitive signals for identifying low antigenic expression, and the technique has been adapted to the characterization of cells present at very low frequencies. Normal human BM samples from 13 adult healthy volunteers have been analyzed using triple stainings at flow cytometry. The mean percentage of CD34+ cells detected was 0.72 +/- 0.33%; these cells displayed an heterogeneous light-scatter distribution. Most CD34+ cells coexpressed CD38 (96.7 +/- 5.7%), HLADR (81.6 +/- 14.0%), CD33 (84.7 +/- 18.3%), CD13 (84.6 +/- 16.2%) and CD71 antigens (65.5 +/- 9.1%). In addition, almost half of CD34+ cells were CD117+ (60 +/- 26.8%). Only a small proportion of CD34+ cells coexpressed CD4 (15.5 +/- 11.7%, CD36 (31.7 +/- 6.2%), CD61 (16.3 +/- 12.9%), CD41 (6.5 +/- 5.5%) or the lymphoid associated markers CD10 (18.6 +/- 11.8%) and CD19 (12.3 +/- 13.2%). Reactivity for the CD15 antigen was observed in a small population of CD34+HLADR+ cells (11.6 +/- 11.2%) although its intensity of expression was lower than that of the more mature granulocytic cells. No CD34+ cells displayed CD14, CD65, CD20, strong CD22, CD3 and CD56 antigens. Accordingly, most adult bone marrow CD34+ cells appeared to be committed to the myeloid lineage (CD13+/CD33+) and displayed an intermediate-to-large FSC/SSC while the lymphoid-committed CD34+ cells (CD19+, CD10+) were in a minority with low FSC/SSC values. By triple marker stainings several phenotypes of CD34+ precursor cells were found to be either undetectable or present at very low frequencies (< 1 x 10(-3)) in the normal human adult bone marrow. These data may be of great value for defining leukemia 'associated' phenotypes used to detect minimal residual disease in adult acute leukemia patients.
Leukemia 1995 Nov
PMID:Phenotypic analysis of CD34 subpopulations in normal human bone marrow and its application for the detection of minimal residual disease. 747 81

In 1985 acute megakaryoblastic leukemia was included in the FAB classification system of hematological neoplasias with the designation of AML M7. It occurs in all age groups with two peaks in distribution. The one is in adults and the other in children 1 to 3 years of age especially in those with Down's syndrome. The diagnosis of AML M7 requires more than 30% of the nucleated bone marrow cells being megakaryoblasts. The more common types of AML MO-M6 have to be excluded by morphological and cytochemical analysis whereas immunology is needed to exclude ALL. The megakaryocytic nature of the leukemia has to be proven by ultrastructural demonstration of platelet peroxidase or by immunological demonstration of CD61, CD42, CD41 on the surface of the leukemic blasts. Megakaryocytic/megakaryoblastic leukemias show a wide morphologic spectrum. In some instance small cells dominate, clearly showing megakaryocytic differentiation with scant amounts of cytoplasm and with nuclei showing dense chromatin. On the other hand, there are cases with larger cells resembling ALL-L2 blasts with moderate amounts of rather basophilic cytoplasm which in some instances contain azurophilic granules. Cytoplasmic blebs and protrusions are the most prominent feature of many cases. The nuclei of these cells are round with more finely reticulated chromatin and with prominent nucleoli. The megakaryoblastic nature of these cells can be suggested by morphology. However, according to our experience there are cases of c-ALL with the very same morphologic picture. Consequently, immunologic phenotyping of these cases is necessary in any instance. Cytochemistry is of limited diagnostic value in megakaryoblastic leukemias. Usually it is used to exclude the more common types of leukemia.
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PMID:Acute megakaryoblastic leukemia. 749 59

This study assesses the value of immunologic and ultrastructural methods in disclosing the lineage commitment of cells from acute leukemias (ALs). Two hundred and fifty-one ALs were characterized morphologically, cytochemically, and immunologically. Myeloperoxidase (MPO) positivity in > 3% of blasts was regarded as evidence of the myeloid origin of leukemic cells, cytoplasmic CD22 (cCD22) expression was taken as an indication for B-lineage acute lymphoblastic leukemia (ALL), and CD3+ (membrane or cytoplasmic) cases were classified as T-ALL. Diagnosis of minimally differentiated acute myeloid leukemia (AML-M0) was made when blast cells had undifferentiated features by light microscopy, reacted with at least one of the antibodies to myeloid-specific antigens (CD13, CD33, MPO), and lacked CD19, cCD22, and c/mCD3. Megakaryoblastic differentiation was demonstrated by the expression of CD41 and/or CD61. Following these criteria, 209 cases were classified as acute myeloid leukemia (AML) and 39 as ALL. Expression of lymphoid antigens was detected in 45% of AML cases and 30% of ALLs showed myeloid antigens. One case was regarded as a true biphenotypic leukemia because of the combined expression of MPO and CD33 for the myeloid lineage, and cCD3, CD2, and CD5 for the T-cell lineage. Two cases lacked signs of myeloid or lymphoid differentiation and were studied by electron microscopy methods. One displayed platelet peroxidase (PPO) activity and was classified as a megakaryoblastic variant, one other reacted with anti-CD33 and was considered AML-M0. We conclude that light microscopy and standard immunologic methods can accurately demonstrate the lineage orientation in greater than 99% of ALs. Integration with ultrastructural analysis can define the cell nature of virtually all cases of AL.
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PMID:Lineage identification of acute leukemias: relevance of immunologic and ultrastructural techniques. 755 58

Individuals with Down syndrome have an increased incidence of leukemia compared to the general population. In addition, Down syndrome children may acquire a myeloproliferation that resembles acute leukemia that undergoes a spontaneous, durable remission. To clarify the relationship between these two disorders, the morphologic, immunophenotypic and cytogenetic characteristics of 28 patients with Down syndrome and the morphologic manifestations of acute leukemia were examined. Three cytomorphological groups were discerned. The first two groups consisted of five patients with acute lymphoblastic leukemia (group I) and three patients with acute myeloid leukemia (group II). These leukemias resembled those of non-Down individuals. The third and largest group (group III) consisted of 20 cases of acute myeloid leukemia that showed prominent megakaryocytic and/or erythroid differentiation and occurred in children under 6 years of age. The blasts in this group were non-reactive for myeloperoxidase or non-specific esterase and expressed CD7, CD34 and CD36 with variable expression of CD61, CD13 and CD33. Four patients in this group had an acquired trisomy 8. Four group III leukemias underwent a durable, spontaneous remission within 2 months of diagnosis. There were no morphologic differences between those leukemias in this group that progressed and those that remitted; however, all remissions occurred in newborns. It is concluded that Down syndrome children acquire a characteristic acute myeloid leukemia that has prominent megakaryocytic and/or erythroid differentiation and an unusual immunophenotype. This group of leukemias may undergo a durable, spontaneous remission in the newborn period.
Leukemia 1995 Sep
PMID:Acute leukemia and the transient myeloproliferative disorder associated with Down syndrome: morphologic, immunophenotypic and cytogenetic manifestations. 765 8

In this study we describe the morphologic and immunohistochemical evaluation of bone marrow biopsies from 14 patients with therapy-related myelodysplastic syndromes (t-MDS). We employed CD34, anti-HLA-Dr, anti-elastase, CD68, anti-glycophorin, CD61 monoclonal antibodies immunostaining, and enzyme histochemistry for chloroacetate esterase. Moreover, we used PC10, a MAb raised against the proliferating cell nuclear antigen, to study the proliferative capacity of these marrows. Our data suggest that diagnosis of refractory anemia with excess of blasts (versus chronic myelomonocytic leukemia), the abnormal localization of immature precursors, marrow fibrosis, and augmented CD34 expression in the bone marrow biopsy are ominous prognostic factors at a statistically significant level (p < 0.0005). A combined morpho-immunohistochemical analysis of bone marrow biopsy correctly classifies t-MDS cases according to the biologic and clinical aggressiveness.
Leukemia 1993 Jun
PMID:Therapy-related myelodysplastic syndromes: FAB classification, bone marrow histology, and immunohistology in the prognostic assessment. 768 97

A 25-year-old man noted swelling of the right cervical lymph nodes in October 1983. Diagnosis of malignant lymphoma was made on the basis of pathological examination of biopsies. Despite both chemotherapy and irradiation treatment, blast cells appeared in the peripheral blood and bone marrow in April 1984. Immunophenotypic analysis demonstrated that the blasts in the patient's peripheral blood expressed CD13, CD33, CD41a, and no markers for T or B lymphocytes, suggesting that he had been suffering from megakaryocytic sarcoma. We established a new cell line derived from the blasts in the peripheral blood, designated KH184. KH184 cells expressed glycoprotein (GP) Ib (CD42b) and GPIIb/IIIa (CD41a), while platelet peroxidase (PPO) activity was negative in an ultrastructural study. Both Northern blot and flow cytometric analysis of surface antigens and DNA content revealed that treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) did not induce the maturation of these cells. Various cytokines such as interleukin 3 (IL-3), interleukin 6 (IL-6), and leukemia inhibitory factor (LIF) had no effect in promoting the growth of KH184 cells. KH184 cells expressing CD41a seem to possess unusual characteristics. KH184 cells, human GPIIb- and GPIIIa-positive leukemia cells, which lack response to TPA-induced differentiation, provide a new and unique model for the characterization of factors that are implicated in the terminal differentiation of megakaryocytes, and should aid in studies of the mechanism underlying the occurrence of megakaryocytic sarcoma.
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PMID:Extramedullary tumor as presentation of leukemia: establishment of a new human GPIIb- and GPIIIa-positive leukemia cell line. 816 81

Neonates with Down's syndrome may develop a transient myeloproliferative disorder (TMPD) which on presentation is indistinguishable from acute leukemia, with the difference manifest only on follow-up. The clinical course is one of spontaneous remission in TMPD and relentless progression in leukemia. We describe a Down's neonate presenting with hyperleucocytosis and circulating blasts which were positive for CD34, myeloid (CD33), megakaryocytic (CD41, CD42b, CD61), and T-lineage (CD3, CD7), but not B-lineage, associated antigens. Clonal rearrangement of the T-cell receptor beta (TCR beta) gene was found, with the immunoglobulin heavy chain gene in germline configuration, showing the disease to be a clonal proliferation of a multipotential stem cell involving the myeloid and T lineages. Dual-colour flow cytometric DNA ploidy analysis of CD41 positive blasts showed initially a predominant 2N population, but polyploidization to 6N and 8N cells was found on follow-up, concomitant with a progressive decrease in circulating blasts, suggesting maturation of the abnormal clone and a provisional diagnosis of TMPD. This was shown by the eventual resumption of normal haemopoiesis with the disappearance of blasts and the clonally rearranged TCR beta gene.
Leukemia 1993 Oct
PMID:Transient myeloproliferative disorder in a Down's neonate with rearranged T-cell receptor beta gene and evidence of in vivo maturation demonstrated by dual-colour flow cytometric DNA ploidy analysis. 841 31

In our report, myelofibrosis in children is discussed and two cases of acutely developing myelofibrosis in association with acute megakaryoblastic leukaemia (M7) are presented. In the first case (girl, 34 months), it was acute myelofibrosis of hypocellular marrow. Diagnosis of M7 was confirmed by positive reaction of blasts from peripheral blood with CD42 and CD61 monoclonal antibodies. In the other child (girl, 5 years old), Ph1(+) chronic myeloid leukaemia diagnosed 22 months earlier transformed to M7. Similar to the first case, no marrow aspirate could be obtained and the diagnosis of M7 was made by the bone marrow histology that showed the presence of grossly fibrosed, hypercellular marrow with a large number of dysplastic, maturing megakaryocytes. Neither of the children had Down's syndrome. Although according to FAB classification both cases represent the same haematological entity, their clinical and histopathological presentations are very different.
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PMID:Acute myelofibrosis in children: report on two cases. 862 48

The present review has summarized the expression, production and effects of the human interleukins (IL) 1-11 and myelopoietic colony stimulating factors (CSF) in the established myeloid leukemia cell lines and in cells from patients with acute myeloid leukemia as well as the oncogene expression reported in these myeloid leukemia cell lines. The genetic dissection of leukemic myelopoiesis may provide new perspectives for the control of myeloid leukemias. Based on their expression of phenotypic markers (e.g., surface antigens, cytochemical staining, etc.), myeloid cell lines can be further subdivided into myelogenous, monocytic, erythroid and megakaryoblastic leukemia cell lines. Due to the close relationship of erythroid and megakaryoblastic progenitor cells and to the existence of a probably common precursor cell giving rise to these two different cell lineages, many megakaryoblastic cell lines express erythroid markers (e.g., expression of hemoglobin or glycophorin A) and conversely cell lines with a predominant erythroid profile might display megakaryoblastic features (e.g., platelets peroxidase or glycoproteins CD41, CD42b or CD61). The recent cloning of the specific cytokine: thrombopoietin (TPO) and its receptor generated a strong interest in these particular myeloid cell lines that are discussed in more detail in the present review. Both normal and leukemic megakaryocytopoiesis are stimulated by granulocyte-macrophage colony stimulating factor (GM-CSF), IL-3, GM-CSF/IL-3 fusion protein, IL-6, IL-11 and TPO but inhibited by IL-4, interferon-alpha (IFN-alpha) and IFN-gamma. Human megakaryoblastic leukemia cell lines have common biological features: high expression of the megakaryocytic specific antigen (CD41); high expression of early myeloid antigens (CD34, CD33 and CD13); constitutive expression of IL-6 and platelet-derived growth factor; a complex karyotype picture; expression of c-kit (the stem cell factor receptor); growth-dependency or -stimulation by IL-3 and/or GM-CSF; and in vivo tumorigenicity in mice associated with marked fibrosis. Whereas numerous chemical and biologic agents induce granulocytic and/or monocytic differentiation of myeloid leukemia cell lines, only a few agents including phorbol myristate acetate, vitamin D3, IFN-alpha, IL-6 and thrombin have been reported to induce megakaryocytic differentiation in the megakaryoblastic leukemia cells.
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PMID:Interleukins and colony stimulating factors in human myeloid leukemia cell lines. 875 Jun 18

For the cell type diagnosis of leukemia in adult patients, particularly when the sampling of bone marrow is difficult, the study of peripheral blood leukocytes (PBLs) by immuno-electron microscopy provides significant information, as illustrated here in two cases of hairy cell leukemia and seven cases tentatively identified as megakaryoblastic leukemia (M7). Indirect immunogold labeling with the B-ly7 monoclonal antibody (CD103) proved valuable in confirming the diagnosis of hairy cell leukemia. Immunogold labeling for the GpIIIa platelet glycoprotein (CD61) was used in cases where the light microscopy of blood films revealed possible megakaryoblastic leukemia. Under the electron microscope, however, the CD61 positive cells showed, in almost all cases, a wide spectrum of megakaryopoietic differentiation which made the diagnosis of M7 questionable. Most of the CD61 positive cells featured cytoplasmic differentiation markers such as alpha granules and demarcation membranes, further confirming the presence of circulating megakaryocythemia, a phenomenon described many years ago in various myeloproliferative disorders. It is suggested, therefore, that many of these cases should not be identified as true megakaryoblastic leukemias.
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PMID:Immunogold labeling for the diagnosis of leukemia by transmission and scanning electron microscopy. 881 97


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