Inzidenz und Überleben bei Leukämien in Deutschland nach aktuellen standardisierten Kategorien

Nennecke, Alice; Wienecke, Antje; Kraywinkel, Klaus

doi:10.1007/s00103-013-1869-0

Cited by 9 publications

(4 citation statements)

References 16 publications

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“…In the past years, survival of MPN patients, especially for PV and ET subtypes has improved [ 13 ], yet the relative 5-year survival for MPN patients in Germany decreases from 92.3 % at ages 14–49 years to 63 % at 70+ years of age [ 43 ]. Reasons for the higher mortality rates in elderly patients were, in particular, thrombotic/thromboembolic events [ 10 , 14 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Bleeding, thrombosis, and anticoagulation in myeloproliferative neoplasms (MPN): analysis from the German SAL-MPN-registry

et al. 2016

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BackgroundPatients with Ph-negative myeloproliferative neoplasms (MPN), such as polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are at increased risk for thrombosis/thromboembolism and major bleeding. Due to the morbidity and mortality of these events, antiplatelet and/or anticoagulant agents are commonly employed as primary and/or secondary prophylaxis. On the other hand, disease-related bleeding complications (i.e., from esophageal varices) are common in patients with MPN. This analysis was performed to define the frequency of such events, identify risk factors, and assess antiplatelet/anticoagulant therapy in a cohort of patients with MPN.MethodsThe MPN registry of the Study Alliance Leukemia is a non-interventional prospective study including adult patients with an MPN according to WHO criteria (2008). For statistical analysis, descriptive methods and tests for significant differences as well as contingency tables were used to identify the odds of potential risk factors for vascular events.ResultsMPN subgroups significantly differed in sex distribution, age at diagnosis, blood counts, LDH levels, JAK2V617F positivity, and spleen size (length). While most thromboembolic events occurred around the time of MPN diagnosis, one third of these events occurred after that date. Splanchnic vein thrombosis was most frequent in post-PV-MF and MPN-U patients. The chance of developing a thromboembolic event was significantly elevated if patients suffered from post-PV-MF (OR 3.43; 95 % CI = 1.39–8.48) and splenomegaly (OR 1.76; 95 % CI = 1.15–2.71). Significant odds for major bleeding were previous thromboembolic events (OR = 2.71; 95 % CI = 1.36–5.40), splenomegaly (OR = 2.22; 95 % CI 1.01–4.89), and the administration of heparin (OR = 5.64; 95 % CI = 1.84–17.34). Major bleeding episodes were significantly less frequent in ET patients compared to other MPN subgroups.ConclusionsTogether, this report on an unselected “real-world” cohort of German MPN patients reveals important data on the prevalence, diagnosis, and treatment of thromboembolic and major bleeding complications of MPN.

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Section: Discussionmentioning

confidence: 99%

Bleeding, thrombosis, and anticoagulation in myeloproliferative neoplasms (MPN): analysis from the German SAL-MPN-registry

et al. 2016

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“…Thus, making leukemia the ninth most common type of cancer in the United States of America. These trends are comparable with current data available for Germany (Nennecke et al 2014).…”

Section: Epidemiologysupporting

confidence: 90%

“…Focussing exclusively on the subtype of acute myeloid leukemia (AML), the incidence remains at 3,1 cases per 100.000 of the German population per year with a clear correlation to a higher age (Nennecke et al 2014). The median age of initial diagnosis is 66 years, with 70 % of patients being older than 55 years (Howlader et al 2014b…”

Section: Epidemiology Of Acute Myeloid Leukemia (Aml)mentioning

confidence: 99%

Minimal residual disease detection of the fusion protein DEK/CAN in t(6;9)(p23;q34) positive acute myeloid Leukemia and identification of target genes and key pathways for leukemogenesis

Ferrara¹

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Acute myeloid leukemia (AML) is a neoplastic disease of an early myeloid precursor cell in hematopoiesis. It leads to the accumulation of monoclonal cells in the bone marrow and the peripheral blood, showing a differentiation block and deregulated self-renewal. Frequently, the leukemic cells exhibit genetic aberrations with reciprocal chromosomal translocations. These translocations induce the formation of a fusion protein, that can lead to new cellular functions and a transformation into a leukemic cell. Common chromosomal translocation in AML are t(8;21) or t(15;17), which cause the formation of the fusion proteins AML1/ETO and PML/RARα and determine the leukemic phenotype of the AML. The translocation t(6;9) leads to the formation of the fusion protein DEK/CAN and is of special interest, because of its association with mostly young patients and a very aggressive course of the disease. The fusion product induces leukemia in a small subset of hematopoietic stem cells, but its mechanism of leukemogenesis is greatly unknown. The intention of this work was to characterize the DEK/CAN-induced AML on a molecular genetic level to gain a deeper understanding of the disease pathogenesis. Therefore, gene expression analysis with polymerase chain reaction (PCR) and microarray analysis was performed. To detect DEK/CAN in different cell lines by PCR and real-time quantitative PCR (qPCR), specific primers and probes were designed, and a standardized workflow was established. Emphasis was placed on the optimization of RNA isolation, DNase treatment, cDNA synthesis with following PCR and qPCR, which enabled the detection of the fusion product DEK/CAN in the cell lines 32B, Phoenix and FKH-1. To quantify the fusion product DEK/CAN, the method of qPCR with absolute and relative quantification was used. Absolute quantification enabled the calculation of an exact copy number of the fusion transcript DEK/CAN with a detection limit of 50 copies/µl at a sensitivity of 10-6, which is of importance in determining the minimal residual disease (MRD) of patients with DEK/CAN-positive AML. MRD detection by qPCR is a highly sensitive diagnostic method to identify leukemic cells, even in low cell counts. This enables a thorough evaluation of the treatment response and allows an early detection of changes in the MRD level as part of the remission control. Additionally, a microarray gene expression analysis was performed to identify alterations in relevant target genes and associated signaling pathways in DEK/CAN-positive cells. Because of DEK/CAN’s potential to induce leukemia in a subset of hematopoietic stem cells, Sca+/Lin- cells of the bone marrow of C57Bl/6 mice were used and transfected with the gene products DEK/CAN and PML/RARα. Microarray analysis led to the identification of 16 different genes of interest, which demonstrated significant alterations of gene expression in DEK/CAN-positive cells. They were validated and quantified with TaqMan assay assisted qPCR. The elevated expression of the transcription factors TRIM25, HIF1α and ATF2, in DEK/CAN-positive cells, indicated an altered transcription factor activity and interaction with DNA in the nucleus. The localization of DEK/CAN in the nucleus emphasizes this assumption. Also, the upregulated expression of the nuclear export receptor XPO1 suggested changes in nuclear transport processes and impaired export activity in DEK/CAN-positive cells. Furthermore, the results demonstrated changes of gene expression in genes that are involved in the JAK/STAT signaling pathway. PTPRC, the Protein Tyrosine Phosphatase Receptor Type C, functions as a direct inhibitor of JAKs (Janus Kinases) and STATs (Signal Transducers and Activators of Transcription) and their associated signaling pathway. It was shown that the gene expression of PTPRC was significantly reduced in DEK/CAN-positive cells. This allowed the assumption, that the reduced expression of PTPRC led to a loss of inhibition and thus a consecutive hyperactivation of the JAK/STAT signaling pathway. This hypothesis was supported by an independent activation of PIM1, a target gene of STAT5 and the activation of LMO2, a direct target gene of JAK2. In addition, the transmembrane receptor CSF1R, which is directly involved in STAT activation, also showed an upregulation in gene expression. The results of this work show an activation of the JAK/STAT signaling pathway in DEK/CAN-positive cells, which may be a key mechanism in DEK/CAN-induced leukemogenesis. Considering treatment options in the future, the addition of targeted therapy, such as pan-JAK inhibitors, to the standard therapy, could be a chance to improve the overall survival rate and the prognosis of t(6;9)-positive AML.

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“…B. Pulte et al 2017, Nennecke et al 2014a, 2014b, die Analysen zur Lebensqualität von Langzeit-Überlebenden im Rahmen der CAESAR-Studie (Arndt et al 2017, Koch-Gallenkamp et al 2016, Zeißig et al 2015, Koch et al 2014, zur Erhebung der Risikofaktoren bei Brustkrebspatientinnen (Schmidt et al 2008) 2014): Fear of recurrence in long-term breast cancer survivors-still an issue. Results on prevalence, determinants, and the association with quality of life and depression from the cancer survivorship-a multi-regional population-based study.…”

Section: Hamburgisches Krebsregisterunclassified

Nachhaltige StadtGesundheit Hamburg

2018

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Inzidenz und Überleben bei Leukämien in Deutschland nach aktuellen standardisierten Kategorien

Cited by 9 publications

References 16 publications

Bleeding, thrombosis, and anticoagulation in myeloproliferative neoplasms (MPN): analysis from the German SAL-MPN-registry

Bleeding, thrombosis, and anticoagulation in myeloproliferative neoplasms (MPN): analysis from the German SAL-MPN-registry

Minimal residual disease detection of the fusion protein DEK/CAN in t(6;9)(p23;q34) positive acute myeloid Leukemia and identification of target genes and key pathways for leukemogenesis

Nachhaltige StadtGesundheit Hamburg

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