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1.
Ann Hematol ; 97(2): 335-342, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29151133

RESUMEN

In contrast to the evidence regarding azacitidine (Aza), there is limited knowledge about the combination of decitabine (DAC) and donor lymphocyte infusions as salvage therapy for relapse after allogeneic stem cell transplantation (allo-SCT) so far. We retrospectively analyzed data of 36 patients with hematological (n = 35) or molecular relapse (n = 1) of acute myeloid leukemia (AML, n = 29) or myelodysplastic syndrome (MDS, n = 7) collected from 6 German transplant centers. Patients were treated with a median of 2 cycles DAC (range, 1 to 11). DAC was the first salvage therapy in 16 patients (44%), whereas 20 patients (56%) had previously received 1 to 5 lines of salvage therapy including 16 of them had been treated with Aza. In 22 patients (61%), a median of 2 DLI per patient (range, 1 to 5) was administered in addition to DAC. As a result, overall response rate was 25% including 6 complete remissions (CR, 17%) and 3 partial remissions (PR, 8%). Three patients within the first-line group achieved CR, while also 3 patients receiving DAC as second-line treatment reached CR including 2 patients with previous Aza failure. Median duration of CR was 10 months (range, 2 to 33) and no patient relapsed so far. The 2-year OS rate was 11% (± 6%) without any difference between first-line and pretreated patients. Incidence of acute and chronic graft-versus-host disease was 19 and 5%. Taken together, DAC exerts clinical efficacy in patients with AML or MDS relapsing after allo-SCT and is able to induce durable remissions in individual patients suggesting that DAC may be an alternative to Aza or even a second choice after Aza failure.


Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Azacitidina/análogos & derivados , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/terapia , Transfusión de Linfocitos , Síndromes Mielodisplásicos/terapia , Adulto , Anciano , Azacitidina/uso terapéutico , Decitabina , Femenino , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/inmunología , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/patología , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Terapia Recuperativa/métodos , Análisis de Supervivencia , Trasplante Homólogo , Resultado del Tratamiento
3.
J Med Genet ; 50(2): 108-17, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23339109

RESUMEN

BACKGROUND: Investigation of X-chromosome inactivation patterns (XCIP) by determination of differential CpG-methylation has been widely applied for investigation of female cell clonality. Using this approach the clonal origin of various tumours has been corroborated. Controversially, strong age-related increase of peripheral blood (PB) cell clonality in haematologically healthy female subjects was reported. Recently, transcriptional XCIP ratio analysis challenged these results and questioned the suitability of methylation based clonality assays. METHODS: To reinvestigate XCIP-skewing in CD34, low-density mononuclear bone marrow (BM) as well as PB cells from healthy female subjects and patients with myelodysplastic syndromes (MDS), we established a transcriptional assay using pyrosequencing technique for quantification of single nucleotide polymorphism allele frequencies, representative for XCIP ratios. RESULTS: Our assay provides high sensitivity for XCIP ratio assessment as determined by standard curves, reproducibility, inter-marker correlation as well as correlation with the DNA-methylation based human androgen receptor (HUMARA) assay. Notably, in agreement with most studies investigating this issue, significant age-related increase of XCIP skewing in PB cells from healthy elderly female subjects was confirmed. Moreover, XCIP ratio analysis suggests even stronger clonal manifestation in BM and CD34 cells. In MDS, XCIP skewing levels were distinctively elevated as compared with controls of similar age and higher degrees were associated with poor clinical outcome. CONCLUSIONS: Transcriptional clonal profiling via pyrosequencing allows accurate assessment of XCIP ratios, confirms the validity of the DNA-methylation based HUMARA assay and reveals important insights into ageing healthy and myelodysplastic haematopoiesis.


Asunto(s)
Síndromes Mielodisplásicos/genética , Análisis de Secuencia de ADN/métodos , Inactivación del Cromosoma X/genética , Factores de Edad , Anciano , Anciano de 80 o más Años , Antígenos CD34/genética , Células de la Médula Ósea , Femenino , Hematopoyesis , Humanos , Polimorfismo de Nucleótido Simple , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
4.
Eur J Cancer ; 196: 113436, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38008033

RESUMEN

BACKGROUND: Secondary central nervous system lymphoma (SCNSL) confers a dismal prognosis and treatment advances are constrained by the lack of prospective studies and real-world treatment evidence. METHODS: Patients with SCNSL of all entities were included at first diagnosis and patient characteristics, treatment data, and outcomes were prospectively collected in the Secondary CNS Lymphoma Registry (SCNSL-R) (NCT05114330). FINDINGS: 279 patients from 47 institutions were enrolled from 2011 to 2022 and 243 patients (median age: 66 years; range: 23-86) were available for analysis. Of those, 49 (20 %) patients presented with synchronous (cohort I) and 194 (80 %) with metachronous SCNSL (cohort II). The predominant histology was diffuse large B-cell lymphoma (DLBCL, 68 %). Median overall survival (OS) from diagnosis of CNS involvement was 17·2 months (95 % CI 12-27·5), with longer OS in cohort I (60·6 months, 95 % CI 45·5-not estimable (NE)) than cohort II (11·4 months, 95 % CI 7·8-17·7, log-rank test p < 0.0001). Predominant induction regimens included R-CHOP/high-dose MTX (cohort I) and high-dose MTX/cytarabine (cohort II). Rituximab was used in 166 (68 %) of B-cell lymphoma. Undergoing consolidating high-dose therapy and autologous hematopoietic stem cell transplantation (HDT-ASCT) in partial response (PR) or better was associated with longer OS (HR adjusted 0·47 (95 % CI 0·25-0·89), p = 0·0197). INTERPRETATION: This study is the largest prospective cohort of SCNSL patients providing a comprehensive overview of an international real-world treatment landscape and outcomes. Prognosis was better in patients with SCNSL involvement at initial diagnosis (cohort I) and consolidating HDT-ASCT was associated with favorable outcome in patients with PR or better.


Asunto(s)
Neoplasias del Sistema Nervioso Central , Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso , Humanos , Anciano , Estudios Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Rituximab/uso terapéutico , Resultado del Tratamiento , Trasplante Autólogo , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Estudios Retrospectivos , Estudios Observacionales como Asunto
5.
Nat Cancer ; 4(1): 96-107, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36581734

RESUMEN

Patients with cancer are at high risk of severe coronavirus disease 2019 (COVID-19), with high morbidity and mortality. Furthermore, impaired humoral response renders severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines less effective and treatment options are scarce. Randomized trials using convalescent plasma are missing for high-risk patients. Here, we performed a randomized, open-label, multicenter trial ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001632-10/DE ) in hospitalized patients with severe COVID-19 (n = 134) within four risk groups ((1) cancer (n = 56); (2) immunosuppression (n = 16); (3) laboratory-based risk factors (n = 36); and (4) advanced age (n = 26)) randomized to standard of care (control arm) or standard of care plus convalescent/vaccinated anti-SARS-CoV-2 plasma (plasma arm). No serious adverse events were observed related to the plasma treatment. Clinical improvement as the primary outcome was assessed using a seven-point ordinal scale. Secondary outcomes were time to discharge and overall survival. For the four groups combined, those receiving plasma did not improve clinically compared with those in the control arm (hazard ratio (HR) = 1.29; P = 0.205). However, patients with cancer experienced a shortened median time to improvement (HR = 2.50; P = 0.003) and superior survival with plasma treatment versus the control arm (HR = 0.28; P = 0.042). Neutralizing antibody activity increased in the plasma cohort but not in the control cohort of patients with cancer (P = 0.001). Taken together, convalescent/vaccinated plasma may improve COVID-19 outcomes in patients with cancer who are unable to intrinsically generate an adequate immune response.


Asunto(s)
COVID-19 , Neoplasias , Humanos , COVID-19/terapia , SARS-CoV-2 , Inmunización Pasiva/efectos adversos , Resultado del Tratamiento , Sueroterapia para COVID-19 , Anticuerpos Antivirales , Neoplasias/terapia
6.
Eur J Haematol ; 88(2): 144-53, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21967505

RESUMEN

Myelodysplastic syndromes (MDS) are characterized by dyserythropoiesis resulting in anemia. This pathological hallmark is incompletely understood. Notch signaling has been linked to impaired erythropoietic and megakaryopoietic development of CD34+ progenitor cells, but its role in MDS is unclear. We have analyzed the transcriptional activity of Notch pathway elements and its association with the key erythroid factor globin transcription factor 1 (GATA1) and the apoptosis regulatory gene B-cell lymphoma-xl (BCLxl) in MDS. The methylation of GATA1 erythroid promoter CpG dinucleotides flanking cis-regulatory elements, including an N-box suppressor binding site for HES1 and a GATA-box binding site, was examined in normal and MDS erythropoiesis. We have generated a kinetic in vitro model of MDS erythropoiesis using CD34+ bone marrow cells from healthy donors (n = 7) and patients with MDS (low risk: RA/n = 6, RARS/n = 3; high risk: RAEB/n = 4, RAEB-T/n = 2). RNA expression of GATA1, BCLxl, DLK1, Notch1, HES1, and HERP2 was measured by real-time RT-PCR (qPCR). DNA methylation at seven CpG dinucleotides of the GATA1 gene promoter was quantitatively analyzed by pyrosequencing of bisulfite-treated genomic DNA at any specific time point. For the Notch pathway elements, no conclusive expression differences were found between MDS and normal erythropoiesis. But we found steadily up-regulated RNA expression of GATA1 and of BCLxl during late normal erythropoietic differentiation. In contrast, during MDS, erythropoiesis a loss of typical up-regulation of GATA1 and BCLxl was observed. Hypermethylation of CpG dinucleotides flanking the repressor HES1 binding site within the 5' region of GATA1 was detected particularly during late MDS erythropoiesis. Interestingly, decremental GATA1 promotor methylation values were seen during normal erythropoiesis matching GATA1 RNA up-regulation. Our data show that the critical erythropoietic transcription factor GATA1 as well as the antiapoptotic molecule BCLxl fails to be normally up-regulated during MDS erythropoiesis. The higher residual 5'-GATA1 methylation values in MDS erythropoiesis but decremental loss thereof in normal erythropoiesis suggest a gene dose effect for GATA1 during erythropoiesis being finely tuned by CpG methylation. Its dysregulation may contribute to the ineffective erythropoiesis observed in MDS.


Asunto(s)
Epigénesis Genética , Eritropoyesis/genética , Factor de Transcripción GATA1/genética , Síndromes Mielodisplásicos/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Metilación de ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Receptores Notch/metabolismo , Transducción de Señal , Adulto Joven , Proteína bcl-X/genética
7.
Trials ; 22(1): 765, 2021 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-34732236

RESUMEN

BACKGROUND: Overall survival remains poor in older patients with acute myeloid leukemia (AML) with less than 10% being alive after 5 years. In recent studies, a significant improvement in event-free, relapse-free and overall survival was shown by adding gemtuzumab ozogamicin (GO), a humanized antibody-drug conjugate directed against CD33, to intensive induction therapy once or in a sequential dosing schedule. Glasdegib, the small-molecule inhibitor of smoothened (SMO), also showed improved overall survival in patients not eligible for intensive chemotherapy when combined with low-dose cytarabine compared to low-dose cytarabine alone. These findings warrant further investigations in the phase III GnG trial. METHODS/DESIGN: This is a randomized phase III trial with measurable residual disease (MRD) after induction therapy and event-free survival (EFS) as primary endpoints. The two research questions are addressed in a 2 by 2 factorial design. Patients age 60 years and older are upfront randomized 1:1 in one of the two induction arms: GO administered to intensive induction therapy on days 1,4, and 7 versus GO administered once on day 1 (GO-147 versus GO-1), and double-blinded 1:1 in one of the subsequent treatment arms glasdegib vs. placebo as adjunct to consolidation therapy and as single-agent maintenance therapy for six months. Chemotherapy backbone for induction therapy consists of standard 7 + 3 schedule with cytarabine 200 mg/m2 continuously days 1 to 7, daunorubicin 60 mg/m2 days 1, 2, and 3 and high-dose cytarabine (1 g/m2, bi-daily, days 1, 2, and 3) for consolidation therapy. Addressing two primary endpoints, MRD-negativity after induction therapy and event-free survival (EFS), 252 evaluable patients are needed to reject each of the two null hypotheses at a two-sided significance level of 2.5% with a power of at least 85%. ETHICS AND DISSEMINATION: Ethical approval and approvals from the local and federal competent authorities were granted. Trial results will be reported via peer-reviewed journals and presented at conferences and scientific meetings. TRIAL STATUS: Protocol version: 1st version 20.10.2020, no amendments yet. Study initiation on February 16, 2021. First patient was recruited on April 1st. TRIAL REGISTRATION: ClinicalTrials.gov NCT04093505 ; EudraCT 2019-003913-32. Registered on October 30, 2018.


Asunto(s)
Quimioterapia de Inducción , Leucemia Mieloide Aguda , Anciano , Aminoglicósidos/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bencimidazoles , Gemtuzumab , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Persona de Mediana Edad , Compuestos de Fenilurea
8.
Exp Hematol ; 35(5): 712-23, 2007 May.
Artículo en Inglés | MEDLINE | ID: mdl-17577921

RESUMEN

Deregulated epigenetic mechanisms are likely involved in the pathogenesis of myelodysplastic syndromes (MDSs). Which genes are silenced by aberrant promotor methylation during MDS hematopoiesis has not been equivalently investigated. Using an in vitro differentiation model of human hematopoiesis, we generated defined differentiation stages (day 0, day 4, day 7, day 11) of erythro-, thrombo- and granulopoiesis from 13 MDS patients and seven healthy donors. Promotor methylation analysis of key regulatory genes involved in cell cycle control (p14, p15, p16, CHK2), DNA repair (hMLH1), apoptosis (p73, survivin, DAPK), and differentiation (RARb, WT1) was performed by methylation-specific polymerase chain reaction. Corresponding gene expression was analyzed by microarray (Affymetrix, HG-U133A). We provide evidence that p16, survivin, CHK2, and WT1 are affected by promotor hypermethylation in MDSs displaying a selective International Prognostic Scoring System risk association. A methylation-associated mRNA downregulation for specific hematopoietic lineages and differentiation stages is demonstrated for survivin, CHK2, and WT1. We identified a suppressed survivin mRNA expression in methylated samples during erythropoiesis, whereas WT1 and CHK2 methylation-related reduction of mRNA expression was found during granulopoiesis in all MDS risk types. Our data suggest that lineage-specific methylation-associated gene silencing of survivin, CHK2, and WT1 in MDS hematopoietic precursor cells may contribute to the MDS-specific phenotype


Asunto(s)
Diferenciación Celular , Metilación de ADN , Células Madre Hematopoyéticas/metabolismo , Síndromes Mielodisplásicos/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD34/metabolismo , Linaje de la Célula , Quinasa de Punto de Control 2 , Proteínas Inhibidoras de las Quinasas Dependientes de la Ciclina/genética , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Células Madre Hematopoyéticas/patología , Humanos , Proteínas Inhibidoras de la Apoptosis , Masculino , Proteínas Asociadas a Microtúbulos/genética , Persona de Mediana Edad , Homólogo 1 de la Proteína MutL , Síndromes Mielodisplásicos/metabolismo , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Reacción en Cadena de la Polimerasa/métodos , Proteínas Serina-Treonina Quinasas/genética , ARN Mensajero/genética , Survivin , Proteínas WT1/genética
9.
Int J Med Sci ; 3(4): 148-51, 2006 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-17088941

RESUMEN

hCDC4 (FBW7, FBXW7) is a new potential tumor suppressor gene which provides substrate specificity for SCF (Skp-Cullin-F-box) ubiquitin ligases and thereby regulates the degradation of potent oncogenes such as cyclin E, Myc, c-Jun and Notch. Mutations in the hCDC4 gene have been found in several solid tumors such as pancreas, colorectal or endometrial cancer. We carried out a mutation analysis of the hCDC4 gene in 35 samples of patients with Acute Myeloid Leukemia (AML) to elucidate a possible role of hCDC4 mutations in this disease. By direct DNA sequencing and digestion with Surveyor nuclease one heterozygous mutation in the 5' untranslated region of exon 1, transcript variant 3 was detected. Additionally, we could identify a new intronic SNP downstream of exon 10. The new variation was present in 20% of AML samples and was furthermore confirmed in a panel of 51 healthy individuals where it displayed a frequency of 14%. In conclusion we provide first data that in contrast to several solid tumors, mutations in the hCDC4 gene may not play a pivotal role in the pathogenesis of AML. Furthermore, we describe a new intronic polymorphism with high frequency in the intron sequence of the hCDC4 gene.

10.
Exp Hematol ; 38(8): 661-5, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20399247

RESUMEN

OBJECTIVE: Recently, the "epigenetic molecular clock hypothesis" linked increasing DNA methylation in a distinct CpG island in the cardiac-specific homeobox gene (CSX) gene to relative mitotic cell age. To determine mitotic cell age in hematopoietic cells of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients, we assessed differential CSX methylation patterns in these diseases vs age-adjusted healthy controls. MATERIALS AND METHODS: We performed bisulfite pyrosequencing to analyze CSX methylation in CD34(+) and bone marrow (BM) cells from 53 MDS, 62 AML, 77 ALL patients, and 37 controls. RESULTS: Analysis of MDS CD34(+) and BM cells revealed significantly increasing methylation of CSX in controls < MDS low-risk < MDS high-risk < AML. Furthermore, increased differences of CSX methylation between the CD34(+) vs the unselected BM compartment were detected in matched MDS low-risk but not high-risk and AML samples. ALL samples displayed highly elevated CSX methylation levels as compared to controls. CONCLUSIONS: Assessment of mitotic cell age by CSX methylation analysis could reveal novel insights into the distinct progression of hematologic diseases.


Asunto(s)
Antígenos CD34 , Células de la Médula Ósea/metabolismo , Senescencia Celular , ADN de Neoplasias/metabolismo , Leucemia Mieloide Aguda/metabolismo , Mitosis , Síndromes Mielodisplásicos/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Células de la Médula Ósea/patología , Islas de CpG , Metilación de ADN , Proteína Homeótica Nkx-2.5 , Proteínas de Homeodominio/metabolismo , Humanos , Leucemia Mieloide Aguda/patología , Síndromes Mielodisplásicos/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Factores de Transcripción/metabolismo
11.
Leuk Res ; 33(3): 434-42, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18829110

RESUMEN

Aberrant promoter methylation may contribute to the hematopoietic disturbances in myelodysplastic syndromes (MDS). To explore a possible mechanism, we therefore analyzed expression of DNA methyltransferase (DNMT) subtypes kinetics and aberrant promoter methylation of key regulatory genes during MDS hematopoiesis. An in vitro model of MDS lineage-specific hematopoiesis was generated by culturing CD34+ cells from healthy donors (n=7) and MDS patients (low-risk: RA/n=6, RARS/n=3; high-risk: RAEB/n=4, RAEB-T/n=2) with EPO, TPO and GCSF. Promoter methylation analysis of key genes involved in the control of apoptosis (p73, survivin, DAPK), DNA-repair (hMLH1), differentiation (RARb, WT1) and cell cycle control (p14, p15, p16, CHK2) was performed by methylation specific PCR of bisulfite-treated genomic DNA. Expression of DNMT1, DNMT3a and DNMT3b was analyzed and correlated with gene promoter methylation for each lineage at different time points. DNMT expression (all isoforms) was increased during thrombopoiesis whereas elevated DNMT1 level were seen during erythropoiesis. Associations between aberrant promoter methylation and DNMT expression were found in high-risk MDS for all lineages and during erythropoiesis. Hypermethylation of p15, p16, p73, survivin, CHK2, RARb and DAPK were associated with elevated DNMT isoform expression. No general overexpression of DNMT subtype was detected during MDS hematopoiesis. However a negative association of DNMT3a and 3b expression with MDS disease risk (IPSS) could be observed. Our data indicate that all mammalian DNMT isoforms may be involved in the aberrantly methylated phenotype in MDS but seem also to be essential for the differentiation of normal hematopoietic stem cells. In particular elevated DNMT1 expression may in particular contribute to ineffective erythropoiesis in MDS.


Asunto(s)
Diferenciación Celular , ADN (Citosina-5-)-Metiltransferasas/análisis , Metilación de ADN , Eritropoyesis , Células Madre Hematopoyéticas/patología , Síndromes Mielodisplásicos/genética , Regiones Promotoras Genéticas , Apoptosis/genética , Estudios de Casos y Controles , Ciclo Celular/genética , Células Cultivadas , ADN (Citosina-5-)-Metiltransferasa 1 , ADN Metiltransferasa 3A , Reparación del ADN/genética , Hematopoyesis , Humanos , Síndromes Mielodisplásicos/patología , Isoformas de Proteínas/análisis , ADN Metiltransferasa 3B
12.
Exp Hematol ; 37(2): 215-224, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19135900

RESUMEN

OBJECTIVE: Identification of genomic lesions in progenitor cells of patients with myelodysplastic syndrome (MDS) could lead to the discovery of new disease-specific genes and may be of prognostic value. MATERIALS AND METHODS: We carried out a genome-wide mapping of DNA from CD34+ cells of MDS patients with high-resolution 500K single nucleotide polymorphism arrays and a concomitant integration with global gene expression analysis. Thirteen MDS patients were analyzed. RESULTS: Copy number and loss of heterozygosity analyses detected heterozygous deletions on chromosomes 2, 9, 13, 16, 17, and 20 ranging in size from 0.1 megabases (Mba) to 2.1 Mba. Additionally, numerous regions with significant uniparental disomy were detected. Integration of the genomic data with gene expression analysis showed that genes, which were downregulated at least 1.5-fold in regions of significant deletion and uniparental disomy were exclusively downregulated in those samples displaying the aberration. Genomics and gene expression data were confirmed by real-time polymerase chain reaction and variable number tandem repeat analysis. CONCLUSION: High-density genomic mapping of CD34+ bone marrow cells from patients with MDS identifies cryptic genetic lesions and offers new opportunities for the discovery of target genes in MDS by integration with gene expression analysis.


Asunto(s)
Antígenos CD34 , Mapeo Cromosómico , Regulación de la Expresión Génica , Genoma Humano , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/metabolismo , Polimorfismo de Nucleótido Simple , Células Madre/metabolismo , Adulto , Anciano , Secuencia de Bases , Cromosomas Humanos/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Eliminación de Secuencia
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