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1.
Leukemia ; 30(1): 229-37, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26174629

RESUMEN

Aberrant post-transcriptional regulation by microRNAs (miRNAs) has been shown to be involved in the pathogenesis of acute myeloid leukemia (AML). In a previous study, we performed a large functional screen using a retroviral barcoded miRNA expression library. Here, we report that overexpression of miR-9/9* in myeloid 32D cell line (32D-miR-9/9*) had profound impact on granulocyte colony-stimulating factor-induced differentiation. Further in vitro studies showed that enforced expression of miR-9/9* blocked normal neutrophil development in 32D and in primary murine lineage-negative bone marrow cells. We examined the expression of miR-9/9* in a cohort of 647 primary human AMLs. In most cases, miR-9 and miR-9* were significantly upregulated and their expression levels varied according to AML subtype, with the highest expression in MLL-related leukemias harboring 11q23 abnormalities and the lowest expression in AML cases with t(8;21) and biallelic mutations in CEBPA. Gene expression profiling of AMLs with high expression of miR-9/9* and 32D-miR-9/9* identified ETS-related gene (Erg) as the only common potential target. Upregulation of ERG in 32D cells rescued miR-9/9*-induced block in neutrophil differentiation. Taken together, this study demonstrates that miR-9/9* are aberrantly expressed in most of AML cases and interfere with normal neutrophil differentiation by downregulation of ERG.


Asunto(s)
Leucemia Mieloide Aguda/genética , MicroARNs/fisiología , Células Progenitoras Mieloides/metabolismo , Neutrófilos/citología , Transactivadores/genética , Animales , Diferenciación Celular , Regulación Leucémica de la Expresión Génica , Humanos , Leucemia Mieloide Aguda/patología , Ratones , Ratones Endogámicos C57BL , Regulador Transcripcional ERG
3.
Int J Lab Hematol ; 30(6): 526-30, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18983305

RESUMEN

To asses the quality of bone marrow cytology of hospital laboratories in the south-west Netherlands a proficiency testing program was implemented. Two sets of bone marrow and blood smears from two patients were sent to 20 hospital laboratories using a tight time schedule biannually. Required results consisted of differential counts of 500 bone marrow cells and 100 peripheral blood cells, together with the description of morphological abnormalities and final conclusions. Twice a year the collected review data were discussed in a plenary session which was also used for continuous education. Over the past 7 years 30 bone marrow samples were evaluated. The coefficient of variations of specific cells counts was large. The amount of correct conclusions ranged from 12% to 100% (median: 61%). Participant attendance of the meetings was 90-100%. The total cost of this scheme of proficiency testing approximately amounted euro7000 per year. The presented formulae for both proficiency testing and haematopathological/cytological education is feasible and fulfilled the need of the participants.


Asunto(s)
Médula Ósea/patología , Técnicas Citológicas/normas , Enfermedades Hematológicas/patología , Enfermedades Hematológicas/diagnóstico , Humanos , Laboratorios de Hospital/normas , Países Bajos , Control de Calidad , Reproducibilidad de los Resultados
4.
Neth J Med ; 66(9): 368-72, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18931397

RESUMEN

A relation between growth hormone (GH) deficiency and immunoglobulin deficiency has been suggested previously in a few cases. We describe a patient with an insulin-like growth factor 1 (IGF-1) deficiency and common variable immune deficiency and briefly review earlier publications on the possible interaction between IGF-1 and the immune system. IGF-1 is the downstream mediator of GH. In this patient, GH and IGF-1 levels were both low. The GH response to a GH-releasing hormone test was normal whereas no subsequent IGF-1 response was seen. In our cohort of 14 patients with hypogammaglobulinaemia, two turned out to have slightly decreased IGF-1 serum levels and one patient with a thymoma had an increased IGF-1 level. Even though IGF-1 may be connected to B lymphocyte differentiation, in this patient we hypothesise there is a common impairment in the IGF-1 and IgG pathways.


Asunto(s)
Inmunodeficiencia Variable Común/sangre , Factor I del Crecimiento Similar a la Insulina/deficiencia , Adolescente , Anticuerpos Antiidiotipos/sangre , Anticuerpos Antiidiotipos/inmunología , Biomarcadores/sangre , Inmunodeficiencia Variable Común/inmunología , Estudios de Seguimiento , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina A/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Masculino , Factores de Tiempo
5.
J Neurol ; 255(6): 828-30, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18446313
6.
J Pathol ; 215(1): 13-20, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18348159

RESUMEN

Several miRNAs have been reported to be associated with immunoglobulin heavy chain (IgH) mutation and ZAP-70 expression status in blood samples of B-cell chronic lymphocytic leukaemia/small lymphocytic lymphoma (B-CLL/SLL). In the bone marrow and lymphoid tissues, proliferation centres (PCs) represent an important site of activation and proliferation of the neoplastic cells, suggesting that these tissues better reflect the biology of CLL than circulating blood cells. We collected 33 lymph nodes and 37 blood CLL samples and analysed IgH mutation status and ZAP-70 expression status. Expression of 15 miRNAs was analysed by qRT-PCR and RNA-ISH. Sixty-three per cent of the lymph node cases contained mutated IgH genes and 49% of the lymph node cases were ZAP-70-positive, and a significant correlation was observed between ZAP-70 expression and IgH mutation status. Of the blood CLL samples, 49% contained mutated IgH sequences. The miRNA expression pattern in CLL lymph node and blood samples was very similar. Three of 15 miRNAs (miR-16, miR-21, and miR-150) showed a high expression level in both blood and lymph node samples. No difference was observed between ZAP-70-positive or -negative and between IgH-mutated or unmutated cases. No correlation was found between miR-15a and miR-16 expression levels and 13q14 deletion in the blood CLL samples. RNA in situ hybridization (ISH) revealed strong homogeneous staining of miR-150 in the tumour cells outside the PCs. In reverse BIC/pri-miR-155 expression was observed mainly in individual cells including prolymphocytes of the PCs. This reciprocal pattern likely reflects the different functions and targets of miR-150 and miR-155.


Asunto(s)
Leucemia de Células B/genética , Leucemia Linfocítica Crónica de Células B/genética , MicroARNs/genética , Proliferación Celular , Distribución de Chi-Cuadrado , Expresión Génica , Genes de Inmunoglobulinas , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Inmunohistoquímica , Hibridación in Situ/métodos , Leucemia de Células B/metabolismo , Leucemia de Células B/patología , Leucemia Linfocítica Crónica de Células B/metabolismo , Leucemia Linfocítica Crónica de Células B/patología , Ganglios Linfáticos/química , Ganglios Linfáticos/patología , MicroARNs/sangre , Mutación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteína Tirosina Quinasa ZAP-70/análisis , Proteína Tirosina Quinasa ZAP-70/sangre
8.
Leukemia ; 14(11): 1876-84, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11069022

RESUMEN

Aberrant expression of the Evi1 (ecotropic virus integration site 1) proto-oncogene has been associated with hematopoietic malignancies in both mice and man. To determine the effect of enforced expression of Evi1 in vivo, we developed a transgenic mouse model utilizing the murine Sca-1 (Ly-6E.1) promoter. Here, we describe the generation and analysis of three independent lines of Evi1 transgenic mice. Transgenic animals of two founder lines developed normally. These mice did not show any obvious hematological abnormalities but showed a significant reduction in the number of bone marrow colony-forming unit erythroid (CFU-E)-derived colonies. This implies a defect of normal erythroid hematopoiesis affecting relatively late erythroid progenitor cells. We also show that when newborn Evi1 transgenic mice of these two lines were infected with Cas-Br-M MuLV, tumor incidence was greatly enhanced in comparison with nontransgenic littermates, indicating an increased susceptibility for leukemia development. Interestingly, analysis of a third founder line revealed that all male progeny consistently displayed severely impaired erythropoiesis with major defects in the bone marrow, spleen and peripheral blood. Taken together, our results present the first evidence of Evi1 disturbing normal erythropoiesis in vivo and provides evidence for cooperative potential of Evi1 in tumor progression.


Asunto(s)
Proteínas de Unión al ADN/fisiología , Leucemia Experimental/etiología , Factores de Transcripción/fisiología , Dedos de Zinc/fisiología , Animales , Antígenos Ly/genética , Células Sanguíneas/patología , Médula Ósea/patología , Proteínas de Unión al ADN/genética , Células Precursoras Eritroides/patología , Eritropoyesis/genética , Predisposición Genética a la Enfermedad , Virus de la Leucemia Murina/patogenicidad , Leucemia Experimental/genética , Leucemia Experimental/virología , Proteína del Locus del Complejo MDS1 y EV11 , Masculino , Proteínas de la Membrana/genética , Ratones , Ratones Transgénicos , Modelos Animales , Regiones Promotoras Genéticas , Proto-Oncogenes , Proteínas Recombinantes de Fusión/genética , Infecciones por Retroviridae/genética , Bazo/patología , Factores de Transcripción/genética , Infecciones Tumorales por Virus/genética , Dedos de Zinc/genética
9.
Genes Chromosomes Cancer ; 25(4): 332-8, 1999 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10398426

RESUMEN

In the myelodysplastic syndrome (MDS), cytogenetic abnormalities are often present and can be used as markers in studies for cell lineage involvement. Little is known of the involvement of the megakaryocytic lineage due to the variable ploidy of these cells. We applied dual-color fluorescence in situ hybridization (FISH) to routinely prepared bone marrow (BM) smears of cytogenetically normal patients and seven patients with MDS and monosomy 7 or trisomy 8. Probes specific for the centromeric regions of chromosomes 7 and 8 were detected with fluorescein isothiocyanate (FITC) and Texas Red, respectively. This enabled us to assess the ratio between the numbers of chromosomes 7 and 8 in the polyploid cells. We utilized confocal laser scanning microscopy to count the FITC and Texas Red FISH signals in the different focal layers of the megakaryocytes. Fifty-six megakaryocytes in six normal BM smears were analyzed, giving a mean ratio of 1.0, a standard deviation (SD) of 0.12, and a range of 0.8-1.33. This ratio was applied to evaluation of clonal involvement of individual megakaryocytes in the patients with MDS. In two patients with monosomy 7, the majority of the megakaryocytes were monosomic. In the five patients with trisomy 8, all or a majority of the analyzed megakaryocytes were trisomic. These results add direct evidence that in MDS megakaryocytes are involved in the malignant clone. Genes Chromosomes Cancer 25:332-338, 1999.


Asunto(s)
Megacariocitos/patología , Síndromes Mielodisplásicos/genética , Adulto , Anciano , Anciano de 80 o más Años , Células Clonales , Femenino , Humanos , Hibridación Fluorescente in Situ/métodos , Cariotipificación , Masculino , Microscopía Confocal/métodos , Persona de Mediana Edad , Síndromes Mielodisplásicos/patología
10.
Blood ; 94(1): 39-45, 1999 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-10381496

RESUMEN

The combined use of retinoic acid and chemotherapy has led to an important improvement of cure rates in acute promyelocytic leukemia. Retinoic acid forces terminal maturation of the malignant cells and this application represents the first generally accepted differentiation-based therapy in leukemia. Unfortunately, similar approaches have failed in other types of hematological malignancies suggesting that the applicability is limited to this specific subgroup of patients. This has been endorsed by the notorious lack of response in acute promyelocytic leukemia bearing the variant t(11;17) translocation. Based on the reported synergistic effects of retinoic acid and the hematopoietic growth factor granulocyte colony-stimulating factor (G-CSF), we studied maturation of t(11;17) positive leukemia cells using several combinations of retinoic acid and growth factors. In cultures with retinoic acid or G-CSF the leukemic cells did not differentiate into mature granulocytes, but striking granulocytic differentiation occurred with the combination of both agents. At relapse, the patient was treated with retinoic acid and G-CSF before reinduction chemotherapy. With retinoic acid and G-CSF treatment alone, complete granulocytic maturation of the leukemic cells occurred in vivo, followed by a complete cytogenetical and hematological remission. Bone marrow and blood became negative in fluorescense in situ hybridization analysis and semi-quantitative polymerase chain reaction showed a profound reduction of promyelocytic leukemia zinc finger-retinoic acid receptor-alpha fusion transcripts. This shows that t(11;17) positive leukemia cells are not intrinsically resistant to retinoic acid, provided that the proper costimulus is administered. These observations may encourage the investigation of combinations of all-trans retinoic acid and hematopoietic growth factors in other types of leukemia.


Asunto(s)
Antineoplásicos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Leucemia Promielocítica Aguda/tratamiento farmacológico , Tretinoina/administración & dosificación , Adulto , Cromosomas Humanos Par 11 , Cromosomas Humanos Par 17 , Quimioterapia Combinada , Humanos , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/fisiopatología , Masculino , Inducción de Remisión , Translocación Genética
11.
Leukemia ; 12(2): 150-4, 1998 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9519776

RESUMEN

A 54-year-old woman presented with a severe autoimmune anemia, thrombocytopenia, neutropenia (Evans' syndrome), and CD8+ lymphocytosis, without signs of lymphadenopathy or splenomegaly. A diagnosis of T cell large granular lymphocyte (T-LGL) leukemia was made, based on cytomorphology, the typical CD3+/CD4-/CD8+/CD16+/CD56-/CD57-/HLA-DR(+/-) immunophenotype of the lymphocytosis (9 x 10(9)/l), and biallelic clonally rearranged T cell receptor beta (TCR beta) genes. Clonality of the TCR alphabeta+ T-LGL was also demonstrated with a panel of antibodies against variable domains of TCR beta chains, which showed single Vbeta7.1 expression on the CD3+ T-lymphocytes. After treatment failure with corticosteroids, splenectomy, and cyclophosphamide, respectively, a complete clinical remission was induced and sustained with cyclosporin A. Vbeta7.1/CD8/CD3 triple immunofluorescence stainings appeared to be valuable for titrating the cyclosporin A dosage by monitoring the T-LGL cells during treatment.


Asunto(s)
Anticuerpos Antineoplásicos/análisis , Antineoplásicos/uso terapéutico , Ciclosporina/uso terapéutico , Región Variable de Inmunoglobulina/inmunología , Leucemia Linfoide/tratamiento farmacológico , Leucemia de Células T/tratamiento farmacológico , Anemia Refractaria/sangre , Anemia Refractaria/complicaciones , Femenino , Genes Codificadores de la Cadena beta de los Receptores de Linfocito T , Humanos , Inmunofenotipificación , Leucemia Linfoide/genética , Leucemia Linfoide/inmunología , Leucemia de Células T/genética , Leucemia de Células T/inmunología , Persona de Mediana Edad , Neutropenia/sangre , Neutropenia/complicaciones , Inducción de Remisión , Trombocitopenia/sangre , Trombocitopenia/complicaciones
12.
Blood ; 89(5): 1690-700, 1997 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-9057652

RESUMEN

Patients with myelodysplastic syndrome (MDS) have ineffective in vivo and in vitro erythropoiesis, characterized by an impaired response to erythropoietin (Epo). We examined proliferation and maturation of MDS marrow cells in response to Epo in more detail. Epo-dependent DNA synthesis as well as induction of GATA-1 binding activity in marrow cells from 15 MDS cases were severely reduced as compared with normal bone marrow (NBM). Additionally, the appearance of morphologically identifiable erythroid cells was decreased in MDS cell cultures. These data indicate that both the Epo-dependent proliferation as well as the differentiation induction by Epo is suppressed. To study more upstream events of the Epo signal transduction route we investigated activation of the signal transducer and activator of transcription (STAT) 5. In all 15 MDS samples tested, STAT5 activation was absent or greatly suppressed in response to Epo. In contrast, interleukin-3 induced a normal STAT5 response in MDS cells. Further, in MDS the subset of CD71+ BM cells that is phenotypically similar to Epo-responsive cells in normal marrow, was present. We conclude that the Epo response in MDS is disturbed at an early point in the Epo-receptor (EpoR) signal transduction pathway.


Asunto(s)
Médula Ósea/efectos de los fármacos , Proteínas de Unión al ADN/metabolismo , Eritropoyetina/farmacología , Proteínas de la Leche , Síndromes Mielodisplásicos , Transducción de Señal/efectos de los fármacos , Transactivadores/metabolismo , Factores de Transcripción/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Médula Ósea/metabolismo , Médula Ósea/patología , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Células Cultivadas , Factores de Unión al ADN Específico de las Células Eritroides , Femenino , Factor de Transcripción GATA1 , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/metabolismo , Síndromes Mielodisplásicos/patología , Factor de Transcripción STAT5
13.
Leukemia ; 11(2): 202-5, 1997 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9009081

RESUMEN

Bone marrow from six patients with acute myeloid leukemia (AML) and t(8;21) (q22;q22) or a variant t(8;13;21) was studied by simultaneous analysis of cell morphology and karyotype. Combination of May-Grünwald-Giemsa (MGG) and fluorescence in situ hybridization (FISH) using probes specific for the breakpoint regions of chromosome 8 and 21 allowed us to establish the extent of cell-lineage involvement of the translocation. The translocation was found in all myeloid blasts and in high percentages of the more mature neutrophilic cells. In one patient we could demonstrate the translocation in the eosinophils as well. Erythroblasts and lymphocytes did not show the t(8;21) abnormality. These results indicate that the t(8;21) in AML is restricted to the myeloid (granulocytic) lineage.


Asunto(s)
Cromosomas Humanos Par 21/ultraestructura , Cromosomas Humanos Par 8/ultraestructura , Células Clonales/patología , Células Madre Hematopoyéticas/patología , Leucemia Mieloide Aguda/patología , Células Madre Neoplásicas/patología , Translocación Genética , Adolescente , Adulto , Médula Ósea/patología , Diferenciación Celular/efectos de los fármacos , Femenino , Humanos , Hibridación Fluorescente in Situ , Leucemia Mieloide Aguda/genética , Masculino , Persona de Mediana Edad
14.
Br J Haematol ; 95(3): 531-4, 1996 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-8943897

RESUMEN

Eosinophilia of variable duration, and subsequent progression to granulocytic sarcoma and acute myeloid leukaemia, has been infrequently reported in the literature. We report a patient with eosinophilia and normal cytogenetics who, after 24 years, showed transformation to a granulocytic sarcoma of the brain. Haematological counts were normal but the marrow revealed the cytogenetic abnormality trisomy 8 in 25% of mitoses. Subsequently an AML-M2 developed, showing a complex karyotype including the trisomy 8 in all metaphases. FISH analysis combined with cytological examination identified the trisomy 8 in blasts, eosinophils and dysplastic granulocytes only. Thus progressive leukaemic transformation selectively involved the myeloid compartment.


Asunto(s)
Eosinofilia/complicaciones , Leucemia Mieloide Aguda/etiología , Adulto , Anciano , Neoplasias Encefálicas/etiología , Transformación Celular Neoplásica , Cromosomas Humanos Par 8 , Progresión de la Enfermedad , Humanos , Cariotipificación , Masculino , Persona de Mediana Edad , Trisomía
15.
Blood ; 88(6): 1944-50, 1996 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-8822911

RESUMEN

A subset of leukemic cells is assumed to maintain long-term growth of acute myeloid leukemia (AML) in vivo. Characterization of these AML progenitor cells may further define growth properties of human leukemia. In vitro incubations with 5-fluorouracil (5-FU) have been used for enrichment of normal primitive hematopoietic stem cells. By analogy to normal hematopoiesis, it was hypothesized that primitive leukemic stem cells might be kinetically more inactive than colony-forming cells (colony-forming units-AML [CFU-AML]). To examine this hypothesis, conditions were established for incubation with 5-FU that eliminated all CFU-AML. These conditions selected a 5-FU-resistant AML fraction that was evaluated for its capacity for long-term growth by transplantation into mice with severe combined immunodeficiency (SCID) and long-term culture in the quantitative cobblestone area-forming cell (CAFC) assay. Transplantation of the 5-FU-resistant fraction of four cases of AML into SCID mice resulted in growth of AML. Whereas no CFU-AML survived, 31% to 82% of primitive (week-6) CAFC were recovered from the 5-FU-treated cells. Hematopoietic cells proliferating in the CAFC assay were shown to be leukemic by cytologic, cytogenetic, or molecular analysis. The reduction of AML growth as determined by outgrowth of AML in SCID mice was in the same order of magnitude as the primitive (week-6) CAFC reduction. This indicates that both assays measure closely related cell populations and that the CAFC assay can be used to study long-term growth of AML. These results show a hierarchy of AML cells that includes 5-FU-resistant progenitors. These cells are characterized as primitive (week-6) CAFC and as leukemia-initiating cells in SCID mice.


Asunto(s)
Fluorouracilo/farmacología , Leucemia Mieloide/patología , Células Madre Neoplásicas/efectos de los fármacos , Enfermedad Aguda , Animales , Secuencia de Bases , Cromosomas Humanos Par 8 , Cartilla de ADN/química , Factor Estimulante de Colonias de Granulocitos/genética , Humanos , Leucemia Mieloide/tratamiento farmacológico , Ratones , Ratones SCID , Datos de Secuencia Molecular , Trasplante de Neoplasias , Mutación Puntual , Factores de Tiempo , Trisomía , Células Tumorales Cultivadas
16.
Br J Haematol ; 93(3): 594-600, 1996 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8652379

RESUMEN

The cell morphology and karyotype of bone marrow samples from 24 patients with myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) were studied simultaneously with a combined technique of May-Grünwald-Giemsa (MGG) staining and fluorescence in situ hybridization (FISH) with chromosome-specific DNA probes. This enabled us to investigate cell lineage involvement in three malignant conditions: MDS (n = 12), leukaemia-transformed MDS (LT-MDS) (n = 5) and de novo AML (n = 7). In MDS we found blasts and often significant proportions of mature granulocytic and erythroid cells to be cytogenetically abnormal. Percentages of granulocytic and erythroid cells with cytogenetic aberrations were generally less than those of blasts. These data support the involvement of a transformed pluripotent stem cell that has retained maturation abilities. In two patients with chronic myelomonocytic leukaemia (CMMoL) the clonal involvement of monocytes was predominant. Results in the five patients with LT-MDS were similar to those in MDS. In the bone marrow of five of the seven de novo AML patients the cytogenetic abnormalities were restricted to the blasts and did not include the more mature granulocytic or erythroid populations. In the other two patients with AML, both with a t(8;21) and a loss of the Y chromosome, high percentages of mature neutrophils were cytogenetically abnormal. These patterns of clonal lineage involvement in MDS, LT-MDS, t(8;21) AML and AML appear typical and may be of clinical use, for example, for distinguishing LT-MDS from de novo AML in newly presenting patients.


Asunto(s)
Leucemia Mieloide/patología , Síndromes Mielodisplásicos/patología , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Médula Ósea/patología , Clonación Molecular , Eritroblastos/patología , Femenino , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Leucemia Mieloide/genética , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/genética
17.
Leukemia ; 9(11): 1818-21, 1995 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-7475268

RESUMEN

Bone marrow and blood from three patients with myelodysplastic syndrome (MDS) and monosomy 7 were studied for cell lineage involvement of the chromosomal abnormality. Cytogenetic involvement of the myeloid and erythroid cell lineages in MDS with monosomy 7 has been shown before. Lymphoid subpopulations have also been investigated but generally with negative results. A combined technique of May-Grünwald-Giemsa (MGG) for cell cytology and interphase fluorescence in situ hybridization (FISH) using a chromosome 7 specific DNA probe was applied. Further, immunophenotype and genotype of the cells were simultaneously examined with alkaline phosphatase anti-alkaline phosphatase (APAAP) immunostaining and FISH. The monosomy 7 was found in the blasts and in all or in subpopulations of myeloid and erythroid cells. T cells (CD3+, CD5+) did not appear to be involved. B cells (CD19+, CD22+) showed a normal distribution of FISH spots in two patients. In one patient however the loss of a chromosome 7 was found in approximately 70% of the cells positive for B cell markers including CD79a. The results of this study show that in some cases MDS is a disease arising in a progenitor cell with repopulative abilities restricted to myelopoiesis and erythropoiesis. In other cases, the pluripotent progenitor cells in MDS may show the capacities to differentiate into B lineage lymphoid cells, as well as suggesting that in those instances MDS represents a condition of more primitive transformed hematopoietic ancestor cells.


Asunto(s)
Aberraciones Cromosómicas/genética , Cromosomas Humanos Par 7 , Monosomía/genética , Síndromes Mielodisplásicos/genética , Adulto , Antígenos CD/metabolismo , Niño , Trastornos de los Cromosomas , Células Clonales , Humanos , Inmunofenotipificación , Hibridación Fluorescente in Situ , Síndromes Mielodisplásicos/patología
18.
Br J Haematol ; 88(3): 626-8, 1994 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-7819079

RESUMEN

The choice of treatment of malignant lymphoma may vary considerably and is mainly determined by the pathology and clinical stage. Ultrasonography is currently one of the most sensitive techniques for evaluation of the cervical area. We set out to assess the value of ultrasound imaging when added to conventional staging (physical examination, laryngoscopy, computer tomography of thorax and abdomen, bone marrow cytology and histology) of malignant lymphoma in 47 patients with untreated lymphoma. Hodgkin's disease was present in 14 patients and non-Hodgkin's lymphoma in 33 individuals. The ultrasound results were independently compared with physical examination of the neck. Ultrasonography revealed additional pathological lymph nodes in 6/47 cases (13%). Furthermore, the diagnosis non-Hodgkin's lymphoma could be established in one patient merely as a result of ultrasonography. Ultrasonography of the neck may reveal more pathological lymph nodes in a significant number of patients and may be of value in the initial staging of patients with malignant lymphoma.


Asunto(s)
Enfermedad de Hodgkin/diagnóstico por imagen , Ganglios Linfáticos/diagnóstico por imagen , Linfoma no Hodgkin/diagnóstico por imagen , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Enfermedad de Hodgkin/patología , Humanos , Ganglios Linfáticos/patología , Linfoma no Hodgkin/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias/métodos , Ultrasonografía
19.
Br J Haematol ; 88(1): 196-8, 1994 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-7803244

RESUMEN

We report a patient who developed acute myeloid leukaemia (M2) shortly after successful treatment of a mediastinal germ cell tumour. The leukaemia was preceded by a documented myelodysplastic phase. Complex cytogenetic abnormalities were found in bone marrow and peripheral blood cells including +i(12p), typical of germ cell malignancy. Fluorescence in situ hybridization revealed the presence of +i(12p) in myeloblasts, erythroblasts and neutrophils but not in lymphocytes. This case provides further evidence for a common clonal origin of haematological malignancies and mediastinal germ cell tumours.


Asunto(s)
Carcinoma Embrionario/genética , Cromosomas Humanos Par 12 , Isocromosomas , Leucemia Mieloide Aguda/genética , Neoplasias del Mediastino/genética , Neoplasias Primarias Secundarias , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Embrionario/tratamiento farmacológico , Carcinoma Embrionario/patología , Células Clonales , Humanos , Hibridación Fluorescente in Situ , Leucemia Mieloide Aguda/patología , Masculino , Neoplasias del Mediastino/tratamiento farmacológico , Neoplasias del Mediastino/patología
20.
Blood ; 82(3): 884-8, 1993 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-8338951

RESUMEN

Bone marrow and blood from patients with acute myeloid leukemia and myelodysplastic syndrome were studied by simultaneous analysis of cell morphology and karyotype. A combined technique of May-Grünwald Giemsa (MGG) for cell morphology and fluorescence in situ hybridization (FISH) with chromosome-specific DNA probes for detection of cytogenetic aberrations allowed us to investigate cell-lineage-specific chromosomal abnormalities. We introduced video recordings to examine large numbers of cells. Briefly, evaluation was first performed on MGG slides, during which cell position and morphology were recorded on an S-VHS recorder. Subsequently, the same slides were used for FISH. This resulted in the identification of MGG-stained cells on the video screen and, at the same time, the interpretation of FISH signals in the fluorescence microscope. Specimens of bone marrow or blood samples from four patients with different hematologic malignancies were studied. One of these patients was studied before and after cytotoxic treatment. The gain or loss of chromosomes could be detected easily and morphologically assigned to the blasts in all patients and to a variable proportion of the myelomonocytic lineage in two patients, but not to the lymphocytes. Thus, this method provides new possibilities for investigating the clonality of hematologic malignancies.


Asunto(s)
Médula Ósea/patología , Aberraciones Cromosómicas/diagnóstico , Hibridación in Situ/métodos , Leucemia Mieloide/patología , Síndromes Mielodisplásicos/patología , Enfermedad Aguda , Trastornos de los Cromosomas , Femenino , Humanos , Leucemia Mieloide/genética , Masculino , Síndromes Mielodisplásicos/genética , Grabación en Video
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