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Immunosuppressive therapy leads to transfusion independence for nearly 40% of patients with myelodysplastic syndrome
https://www.healio.com/hematology-oncology/myeloproliferative-neoplasms/news/online/%7B0e194ae3-b0ef-4030-b643-188b4b6df7d5%7D/immunosuppressive-therapy-leads-to-transfusion-independence-for-nearly-40-of-patients-with-myelodysplastic-syndrome

Oct 12th, 2017 - Immunosuppressive therapy helped nearly 40% of patients with myelodysplastic syndrome achieve transfusion independence, according to study results presented at ASH Annual Meeting and Exposition.Patients who achieved response or transfusion independence survived longer, results showed.

A Non-Human Primate CRISPR/Cas9 Model of Clonal Hematopoiesis of Indeterminate Potential Demonstrates Expansion of TET2-Disrupted Clones
http://www.bloodjournal.org/content/130/Suppl_1/117

Jul 12th, 2017 - Recent large-scale genetic screening of human blood cells have identified that somatic mutations associated with clonal expansions commonly arise with aging, even in the absence of cytopenias, myelodysplasia, or leukemia. Loss of function or dominant negative mutations in genes encoding epigenetic modifier enzymes such as DNMT3, TET2, and ASXL1 are most common in this "clonal hematopoiesis of i...

Promising Results of a Phase 1/2 Clinical Trial of Ruxolitinib in Patients with Chronic Myelomonocytic Leukemia
http://www.bloodjournal.org/content/130/Suppl_1/162

Jul 12th, 2017 - Chronic myelomonocytic leukemia (CMML) is a myeloid neoplasm characterized by GM-CSF hypersensitivity, marrow dysplasia, blood monocytosis, and a propensity for acute myeloid leukemia transformation. The overall survival is estimated at 34 months with no drug therapies known to improve survival. We previously reported results of a phase 1 study demonstrating that ruxolitinib, a JAK1/2 inhibitor...

The TGF-β/SMAD Signaling Pathway As a Mediator of NK Cell Dysfunction and Immune Evasion in Myelodysplastic Syndrome
http://www.bloodjournal.org/content/130/Suppl_1/53

Jul 12th, 2017 - Myelodysplastic syndrome (MDS) is a spectrum of clonal hematopoietic disorders affecting the myeloid lineage, characterized by ineffective hematopoiesis and dysplastic features. In about a third of patients, MDS transforms to secondary AML, and for this subgroup the overall survival is dismal. Immune responses against MDS have the potential to prevent disease progression; however, immune evasio...

Global and Targeted RNA-Sequencing Assessment of Cancer Testis Antigen Re-Expression Following Azacitidine in Myelodysplastic Syndromes
http://www.bloodjournal.org/content/130/Suppl_1/1695

Jul 12th, 2017 - Azanucleoside DNA-hypomethylating agents have remarkable clinical activity in myelodysplastic sindromes (MDS) and acute myeloid leukemia (AML), particularly at low, non-cytotoxic doses favoring hypomethylation over cytotoxicity. Cancer/testis antigens (CTAs) encoding immunogenic proteins are normally expressed in the testicles and trophoblastic cells of the ovary and in some malignant tissues: ...

Clinical Implication of Gene Mutations in Children Myelodysplastic Syndromes
http://www.bloodjournal.org/content/130/Suppl_1/1688

Jul 12th, 2017 - Myelodysplastic syndromes (MDS) are typically diseases of older adults. Children with MDS may have distinct molecular and clinical features or reflect a demographic continuum. Method We studied a cohort of 81 pediatric patients with various subcategories of myelodysplastic syndrome and acute myeloid leukemia with myelodysplasia-related changes. All subjects provided informed consent in complian...

Immunological Correlates of Treatment with the CTLA-4 Inhibitor Ipilimumab in Patients with Refractory Myelodysplastic Syndromes (MDS)
http://www.bloodjournal.org/content/130/Suppl_1/1699

Jul 12th, 2017 - Failure of hypomethylating agents (HMAs) in patients with myelodysplastic syndromes (MDS) is associated with dismal survival and there are no currently approved therapies in this setting. We recently presented the results of a multi-center phase 1b study of the immune checkpoint blocker (ICB) ipilimumab given as monotherapy after HMA failure in 29 MDS patients. Eight doses of 3mg/kg administere...

Impact of Transfusion Dependency on Health-Related Quality of Life Outcomes in Newly Diagnosed Patients with Myelodysplastic Syndromes (MDS). Analysis on 669 Patients By Disease Risk
http://www.bloodjournal.org/content/130/Suppl_1/353

Jul 12th, 2017 - There is some evidence indicating that transfusion dependency negatively impact health-related quality of life HRQOL of patients with myelodysplastic syndromes (MDS). However, there is paucity of evidence-based on this relationship across all different disease risk-group categories. Aims: The primary objective of this study is to examine whether transfusion dependency has a different impact on ...

The Use of Immunosuppressive Therapy (IST) in Patients with the Myelodysplastic Syndromes (MDS): Clinical Outcomes and Their Predictors in a Large International Patient Cohort
http://www.bloodjournal.org/content/130/Suppl_1/422

Jul 12th, 2017 - All patients with lower-risk (LR)-MDS experience primary or secondary failure of erythropoiesis-stimulating agents (ESAs), lenalidomide, or hypomethylating agents (HMAs), and there is an unmet need for other active therapies. IST has activity in patients with LR-MDS, but is infrequently used. We studied the clinical outcomes and predictors of response in patients with MDS treated with IST in a ...

Immune Checkpoint Profiling of TP53 Mutant and Wild-Type Myeloid Malignancies: TP53 Mutations Direct Immune Tolerance Via an Immunosuppressive Phenotype
http://www.bloodjournal.org/content/130/Suppl_1/423

Jul 12th, 2017 - Augmenting adaptive immunity through immune checkpoint blockade introduced a paradigm shift in the treatment of cancer patients. Although aberrant mRNA upregulation of several immune checkpoints (e.g. PDL1) has been described in CD34+ cells of myelodysplastic syndrome (MDS) patients compared to normal controls (Yang et al ., 2014), clinical investigations of checkpoint inhibitors in myeloid mal...

Feeding the Fire: The Comorbid and Inflammatory Backdrop of Clonal Hematopoiesis of Indeterminate Potential (CHIP) By Mutation Subtype
http://www.bloodjournal.org/content/130/Suppl_1/426

Jul 12th, 2017 - Clonal hematopoiesis of indeterminate potential/aging (CHIP) is a potential precursor to MDS and myeloid cancer; it is also associated with comorbid cardiometabolic diseases that may be exacerbated by inflammation. The top mutated genes in CHIP are TET2 and DNMT3A (Buscarlet, Blood 2017). Tet2-mutated (deficient) macrophages may contribute to a pro-inflammatory environment (Cull, Exp Hematol 20...

Loss of Toll-like Receptor 2 Results in Accelerated Leukemogenesis in the NUP98-HOXD13 Mouse Model of MDS
http://www.bloodjournal.org/content/130/Suppl_1/48

Jul 12th, 2017 - The myelodysplastic syndromes (MDS) are hematopoietic stem cell (HSC) disorders characterized by ineffective hematopoiesis and a high risk of leukemic transformation. Stem cell transplantation is the only curative treatment available to a subset of patients and is associated with significant morbidity and mortality; thus, new therapies are needed. Multiple studies have shown a correlation betwe...

Bone Marrow Levels of PARP1 mRNA Predict Response to Treatment with 5-Azacytidine in Patients with Myelodysplastic Syndrome
http://www.bloodjournal.org/content/130/Suppl_1/161

Jul 12th, 2017 - Poly [ADP-ribose] polymerase 1 (PARP1) is the major member of a family of nuclear enzymes that participate in DNA repair and gene transcription, by recruiting various proteins involved in DNA repair to sites of DNA damage. PARP1 overexpression has been correlated to poor treatment response in children with acute lymphoblastic leukemia, while PARP1-driven apoptosis is important in patients with ...

Measurement of Increase in Cereblon mRNA Level after Addition of Erythropoietin to Lenalidomide May Predict a Clinical Response to Combination of Both the Drugs in Patients with Lower-Risk Myelodys...
http://www.bloodjournal.org/content/130/Suppl_1/5295

Jul 12th, 2017 - Lenalidomide (LEN) stimulates erythropoietin (EPO) signaling by stabilization of erythropoietin receptor (EPOR) through inhibition of the E3 ubiquitin ligase RNF41 (ring finger protein 41) involved in ubiquitination and subsequent degradation of RNF41 in proteasomes (Basiorka et al. - Cancer Res 76, 3531-3540, 2016). This post-transcriptional mechanism of EPOR stabilization by lenalidomide may ...

A Simple Complete Blood Count to Screen for Myelodysplastic Syndromes
http://www.bloodjournal.org/content/130/Suppl_1/5296

Jul 12th, 2017 - A diagnosis of myelodysplastic syndrome (MDS) is usually suspected upon the discovery of cytopenias (mostly anemia) at complete blood count (CBC). Yet, formal diagnosis requires complementary tests (morphology, bone marrow examination, karyotype, flow cytometry, molecular analyses) which are costly and time consuming. Here, a prospective study was performed over one year in order to investigate...

Icare 1: A Prospective Clinical Trial to Predict Treatment Response Based on Mutanome-Informed Computational Biology in Patients with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS)
http://www.bloodjournal.org/content/130/Suppl_1/4277

Jul 12th, 2017 - Refractory disease remains a challenge in treating patients (pts) with MDS and AML. Despite their widespread use, cytotoxic agents (7+3, HiDAC) and hypomethylating agents (HMAs) fail in the majority of pts, and lenalidomide (LEN) fails in 75% of non-del(5q) MDS. 90% of MDS and AML pts harbor at least one somatic mutation, further contributing to disease complexity. Currently, no comprehensive m...

Acquisition Patterns and Interaction of Molecular, Obvious and Cryptic Cytogenetic Abnormalities in Myelodysplastic Syndromes
http://www.bloodjournal.org/content/130/Suppl_1/4260

Jul 12th, 2017 - The acquisition of cytogenetic aberrations (CA) and/or of molecular mutations (clonal evolution, CE) is known to be associated with poor outcome in pts with myelodysplastic syndromes (MDS) (Jabbour et al, Am J Hematol, 2013; Cevik et al, abstract, Onkologie, 2013). The aim of our study was to identify additional cases with CE by taking cryptic CA, which cannot be detected by conventional chromo...

Examining the Risk of Cardiovascular Disease–Related Mortality in Patients With and MDS/CMML
https://www.ashclinicalnews.org/on-location/examining-risk-cardiovascular-disease-related-mortality-patients-mdscmml/

Feb 2nd, 2018 - Patients with chronic myelomonocytic leukemia (CMML) and myelodysplastic syndromes (MDS) have a higher risk of cardiovascular disease (CVD)–related mortality and cerebrovascular accident (CVA)–related mortality, according to results presented at the 2017 ASH Annual Meeting.

Unrecognized Clonal Hematopoiesis of Indeterminate Potential in Solid Tumors: Implications for Interpretation of Molecular Testing
http://www.bloodjournal.org/content/130/Suppl_1/115

Jul 12th, 2017 - Molecular testing is inevitably performed on patient samples that include not only the tumor being profiled, but also admixed non-lesional tissue such as benign organ parenchyma, stromal cells, and hematopoietic elements. As people age, hematopoietic stem cells may acquire somatic genomic alterations that result in 'clonal hematopoiesis of indeterminate potential' (CHIP), associated with an inc...

Bone Marrow Stem Cells from Patients with Myelodysplastic Syndrome (MDS) Engraft and Migrate in-between the Humanized Niches in Immuno-Compromised Mouse Models
http://www.bloodjournal.org/content/130/Suppl_1/49

Jul 12th, 2017 - Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized mainly by ineffective hematopoiesis. Xenograft models of MDS in immunodeficient mice have been instrumental in improving our understanding of clonal origin and evolution of this disease (Mian & Rouault-Pierre et al., Nat Commun. 2015; Rouault-Pierre & Mian et al Haematologica 2016; Leukemia, 2017); howeve...