Search results for "Myeloid"
showing 10 items of 538 documents
Long-term outcome of older patients with newly diagnosed de novo acute promyelocytic leukemia treated with ATRA plus anthracycline-based therapy
2018
Treatment outcome in older patients with acute promyelocytic leukemia (APL) is lower compared with younger patients, mainly because of a higher induction death rate and postremission non-relapse mortality (NRM). This prompted us to design a risk-and age-adapted protocol (Programa Espanol de Tratamientos en Hematologia (PETHEMA)/HOVON LPA2005), with dose reduction of consolidation chemotherapy. Patients aged >= 60 years reported to the PETHEMA registry and were treated with all-trans retinoic acid (ATRA) plus anthracycline-based regimens according to three consecutive PETHEMA trials that were included. We compared the long-term outcomes of the LPA2005 trial with the preceding PETHEMA tria…
Exploring the MHC-peptide matrix of central tolerance in the human thymus
2013
Ever since it was discovered that central tolerance to self is imposed on developing T cells in the thymus through their interaction with self-peptide major histocompatibility complexes on thymic antigen-presenting cells, immunologists have speculated about the nature of these peptides, particularly in humans. Here, to shed light on the so-far unknown human thymic peptide repertoire, we analyse peptides eluted from isolated thymic dendritic cells, dendritic cell-depleted antigen-presenting cells and whole thymus. Bioinformatic analysis of the 842 identified natural major histocompatibility complex I and II ligands reveals significant cross-talk between major histocompatibility complex-class…
Genome-wide association study identifies novel susceptibility loci for KIT D816V positive mastocytosis
2021
Mastocytosis is a rare myeloid neoplasm characterized by uncontrolled expansion of mast cells, driven in >80% of affected individuals by acquisition of the KIT D816V mutation. To explore the hypothesis that inherited variation predisposes to mastocytosis, we performed a two-stage genome-wide association study, analyzing 1,035 individuals with KIT D816V positive disease and 17,960 healthy control individuals from five European populations. After quality control, we tested 592,007 SNPs at stage 1 and 75 SNPs at stage 2 for association by using logistic regression and performed a fixed effects meta-analysis to combine evidence across the two stages. From the meta-analysis, we identified three …
Outcome of lower-risk patients with myelodysplastic syndromes without 5q deletion after failure of erythropoiesis-stimulating agents
2017
Purpose Most anemic patients with non-deleted 5q lower-risk myelodysplastic syndromes (MDS) are treated with erythropoiesis-stimulating agents (ESAs), with a response rate of approximately 50%. Second-line treatments, including hypomethylating agents (HMAs), lenalidomide (LEN), and investigational drugs, may be used after ESA failure in some countries, but their effect on disease progression and overall survival (OS) is unknown. Here, we analyzed outcome after ESA failure and the effect of second-line treatments. Patients and Methods We examined an international retrospective cohort of 1,698 patients with non-del(5q) lower-risk MDS treated with ESAs. Results Erythroid response to ESAs was 6…
28-year incidence and time trends of childhood leukaemia in former East Germany compared to West Germany after German reunification: A study from the…
2021
Abstract Background The aetiology of childhood leukaemia is largely unknown. Analyses of geographical differences may enhance aetiologic insights. The reunification of Germany in 1990 provides a unique opportunity to evaluate incidence patterns and time trends in two merging countries with substantial lifestyle, social and socioeconomic differences. With this study we provide an extensive assessment of 28-year incidence patterns and temporal trends after the German reunification. Methods We identified all children diagnosed with a lymphoid leukaemia (LL) or acute myeloid leukaemia (AML) before the age of 15 years between 1991 and 2018 using the German Childhood Cancer Registry (N = 14,922),…
SPRED1, a RAS MAPK pathway inhibitor that causes Legius syndrome, is a tumour suppressor downregulated in paediatric acute myeloblastic leukaemia
2013
Constitutional dominant loss-of-function mutations in the SPRED1 gene cause a rare phenotype referred as neurofibromatosis type 1 (NF1)-like syndrome or Legius syndrome, consisted of multiple café-au-lait macules, axillary freckling, learning disabilities and macrocephaly. SPRED1 is a negative regulator of the RAS MAPK pathway and can interact with neurofibromin, the NF1 gene product. Individuals with NF1 have a higher risk of haematological malignancies. SPRED1 is highly expressed in haematopoietic cells and negatively regulates haematopoiesis. SPRED1 seemed to be a good candidate for leukaemia predisposition or transformation. We performed SPRED1 mutation screening and expression status i…
Expression of serologically identified tumor antigens in acute leukemias.
2003
Cancer/testis antigens (CTA) are an expanding family of immunogenic proteins selectively expressed in human neoplasms. As little is known about the expression of serologically identified CTA in leukemias so far, we investigated the expression of 5 CT genes (SSX-1, HOM-MEL-40/SSX-2, HOM-TES-14/SCP-1, SCP-3 and NY-ESO-1) in leukemic blood samples obtained from patients with either acute lymphatic leukemias (ALL) or myelocytic leukemia (AML). RT-PCR-analyses showed no expression of any of the CT-genes in the leukemia samples of 19 patients with AML, whereas frequent expression was found in ALL. In the 17 ALL cases studied, SCP3a, SSX-1, HOM-MEL-40/SXX-2 and HOM-TES-14/SCP-1 were expressed in 4…
Amplification of ETS2 oncogene in acute nonlymphoblastic leukemia with t(6;21;18).
1992
Cytogenetic and molecular studies in a case of acute nonlymphoblastic leukemia (ANLL) are reported in this paper. Bone marrow blasts carried a hypodiploid karyotype with a complex t(6;18;21)(6qter----6p21::21q22----21qter;18qter ----18p11::6p22----6pter; 21pter----21q22::6p21----6p22::18p11----18pte r) and other numerical and structural changes. We studied the organization and the expression of the ETS2 gene which is located on chromosome 21 in order to investigate its possible involvement in the disease. DNA analysis showed a 20-fold amplification of ETS2 sequences; an increase of 3- to 4-fold in the mRNAs level compared to normal was shown by Northern hybridization.
Synergistic Antioncogenic Activity of Azacitidine and Curcumin in Myeloid Leukemia Cell Lines and Patient Samples.
2019
Background/aim Azacitidine (AZA) is a hypomethylating agent used in myeloid neoplasms, however, approximately half of patients show treatment failure or relapse. This in vitro study investigated the effect of the combination of AZA with the natural compound curcumin (CUR) in increasing its efficacy. Materials and methods We analyzed the effects of AZA plus CUR on proliferation, apoptosis, cell cycle and differentiation in myeloid leukemic cell lines (U-937, HL-60, K-562, and OCI-AML3) and bone marrow samples of patients. Results The results showed a synergy between AZA and CUR in all leukemic lines and in most leukemic samples, with a decrease in proliferation and an increase in apoptosis c…
RORC1 Regulates Tumor-Promoting "Emergency" Granulo-Monocytopoiesis
2015
Cancer-driven granulo-monocytopoiesis stimulates expansion of tumor promoting myeloid populations, mostly myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). We identified subsets of MDSCs and TAMs based on the expression of retinoic-acid-related orphan receptor (RORC1/RORγ) in human and mouse tumor bearers. RORC1 orchestrates myelopoiesis by suppressing negative (Socs3 and Bcl3) and promoting positive (C/EBPβ) regulators of granulopoiesis, as well as the key transcriptional mediators of myeloid progenitor commitment and differentiation to the monocytic/macrophage lineage (IRF8 and PU.1). RORC1 supported tumor-promoting innate immunity by protecting MDSCs from …