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Downstream Pathway of AML1-ETO Targeted ARHGEF12 Might be Targetable for Rock Inhibitor to Improve Therapy Outcome
http://www.bloodjournal.org/content/132/Suppl_1/3914

Nov 21st, 2018 - As a transcription factor AML1-ETO modulate gene expression of its targets. Scanning our ChIP-seq data we found AML1-ETO bind to an AML1 binding motif in the promotor region of ARHGEF12. Exploring acute myeloid leukemia (AML) microarray databases we confirmed that the expression of ARHGEF12 was up-regulated consistently in AML1-ETO-positive AML patient samples. To confirmed this finding, we qua...

Drug Monitoring of Asparaginase Activity to Detect Silent Inactivation in Pediatric Acute Lymphoblastic Leukemia Patients Receiving Peg-Asparaginase
http://www.bloodjournal.org/content/132/Suppl_1/3968

Nov 21st, 2018 - Background Asparaginase is a key component of pediatric therapy for Acute lymphoblastic leukemia (ALL). Two formulations available in the USA are pegylated E. coli asparaginase (PEG) and Erwinia chrysanthemi asparaginase (Erwinaze). Hypersensitivity reactions have been observed in ~ 20% of patients receiving PEG. Patients with overt symptoms of hypersensitivity are typically switched to Erwinaz...

Activation of Hottip lncrna Perturbs HSC Function Leading to AML like Disease in Mice
http://www.bloodjournal.org/content/132/Suppl_1/3877

Nov 21st, 2018 - Several HOX loci associated long noncoding RNAs (lncRNAs) have been shown to regulate transcription of HOX genes through influencing epigenetic landscape. Especially, the posterior HOXA domain associated lncRNA HOTTIP acts as an epigenetic regulator that recruits WDR5/MLL complex to coordinate active chromatin modifications and HOXA genes expression in the development of animal digits. Despite ...

Dual Inhibition of Bruton's Tyrosine Kinase and BCL2: A Promising Therapeutic Strategy for Myeloid and Lymphoid Leukemias
http://www.bloodjournal.org/content/132/Suppl_1/214

Nov 21st, 2018 - Background: The identification of effective therapies based on targeted interventions for human cancers faces the challenges of genetic and epigenetic heterogeneity underlying the disease. Large-scale sequencing efforts have uncovered a spectrum of mutations in many hematologic malignancies, suggesting that combinations of agents will be required to treat these diseases effectively. Combinatori...

Acute Neurotoxicity during ALL Therapy Is Associated with Treatment Intensity, Age and Female Sex - an Analysis of SAE Reports from the UKALL 2003 Trial
http://www.bloodjournal.org/content/132/Suppl_1/1379

Nov 21st, 2018 - Background: Neurotoxicity during treatment for childhood acute lymphoblastic leukaemia (ALL) remains a significant problem. It can be acute as in methotrexate stroke-like syndrome, posterior reversible encephalopathy syndrome, or seizures, or may be subacute resulting in chronic neurocognitive defects. Symptomatic and asymptomatic neurotoxicity can affect long-term neurocognitive outcomes (e.g....

Durable Responses to Single-Agent Ibrutinib in Monoallelic—but Not in Biallelic—TP53 Aberrated Patients with Chronic Lymphocytic Leukemia
http://www.bloodjournal.org/content/132/Suppl_1/3111

Nov 21st, 2018 - Introduction In chronic lymphocytic leukemia (CLL), TP53 aberration (TP53ab: del(17p) and/or TP53 mutation) remains the only biomarker directly influencing clinical practice (Blood. 2018;131(25):2745-2760). Further, TP53abs are early events that can lead to acquisition of additional somatic mutations, which suggest genomic instability caused by loss of p53, especially upon therapy. Single-agent...

Dynamic BH3 Profiling Predicts Patient Response and MRD Status in Chronic Lymphocytic Leukemia (CLL) Patients Undergoing Frontline Treatment with Kinase Inhibitor Plus FCR (KI+FCR)
http://www.bloodjournal.org/content/132/Suppl_1/4395

Nov 21st, 2018 - Background We previously found that the combination of ibrutinib (IBR) or duvelisib (DUV) with FCR leads to a high rate of MRD undetectability when given as frontline therapy for younger, fit CLL patients (Davids et al., ASH 2017 and EHA 2018), a strategy we call KI+FCR. However, not all patients achieve deep response, and identifying predictive biomarkers may further improve efficacy rates whi...

Dynamic Personalized Assessment of Outcome in Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
http://www.bloodjournal.org/content/132/Suppl_1/2695

Nov 21st, 2018 - Introduction The combination of tyrosine kinase inhibitors (TKI) with intensive therapy has improved survival in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The survival with the combination of hyper-CVAD (HCVAD) with ponatinib has now reached 3-year overall survival of 75%. Allogeneic stem cell transplant (ASCT) is indicated for patients with Ph+ALL i...

Adoptive Transfers of Plasmacytoid Dendritic Cells after Hematopoietic Stem Cell Transplantation Decrease the Risk Acute Lymphoblastic Leukemia Relapse without Increasing the Risk of Graft-Versus-H...
http://www.bloodjournal.org/content/132/Suppl_1/2053

Nov 21st, 2018 - Despite advances in chemotherapy and hematopoietic stem cell transplantation (HSCT), the outcome of children with relapsed acute lymphoblastic leukemia (ALL) has not significantly improved over the last 2 decades. About 50% of children with relapsed leukemia still die from their disease and ALL is still the first cause of death by cancer in children. A new hope of cure for patients with chemo-r...

Early Detection and Molecular Characterization of Therapy-Related Leukemia in Children Reveals Patterns of Disease Transformation and Guides Future Surveillance Protocols
http://www.bloodjournal.org/content/132/Suppl_1/291

Nov 21st, 2018 - Background Therapy-related myelodysplastic syndrome (MDS) and acute leukemias represent a major cause of non-relapse morbidity and mortality in childhood cancer survivors, and have been associated with exposure to cytotoxic therapies (e.g. radiation, alkylators, topoisomerase inhibitors). Neuroblastoma (NB) patients receive multimodality therapy with intensive chemotherapy, radiation, and immun...

Adverse Events, Patterns of Tumor Lysis Syndrome Prophylaxis and Management, and Dosing Patterns in a Large Cohort of Venetoclax Treated CLL Patients in Community and Academic Settings
http://www.bloodjournal.org/content/132/Suppl_1/4410

Nov 21st, 2018 - Introduction: Venetoclax (Ven), an oral BCL2 inhibitor, is approved for the treatment (tx) of relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Ven is generally well tolerated, and side effects observed in clinical trials have been consistent with other CLL tx. Clinical trials using the approved dose escalation schedule report negligible rates of clinical tumor lysis syndrome (TLS)....

Effects of the Switch to Generic Imatinib in a Cohort of 109 Italian CML Patients - the Gims Study
http://www.bloodjournal.org/content/132/Suppl_1/4266

Nov 21st, 2018 - Introduction. Generic formulations of imatinib mesylate have been introduced in western Europe and the US since 2017 for the treatment of patients affected by Chronic Myeloid Leukemia (CML). Despite bioequivalence data, no independent study to investigate the safety and efficacy of generic imatinib was performed in this region. Aim of the study. The primary goal of the Generic IMatinib Switch (...

AML Cells Express Exclusively the Long Isoform of LEF1 and Are Highly Vulnerable to Blockage of LEF1-β-Catenin Binding
http://www.bloodjournal.org/content/132/Suppl_1/3913

Nov 21st, 2018 - Despite progress in the understanding of the biology of acute myeloid leukemia (AML) in recent years, mortality of the disease is still high. One reason for this is drug resistance of leukemic stem cells (LSCs), which are responsible for leukemic growth and relapse. Thus, there is great interest in understanding factors driving LSCs and in key differences between normal hematopoietic stem cells...

An Epigenetic Mitotic Score Tracks the Proliferative History and Capacity of CLL Samples at Diagnosis and Is Associated with Clinical Outcome
http://www.bloodjournal.org/content/132/Suppl_1/1842

Nov 21st, 2018 - Background: DNA methylation has been extensively described to be related with gene regulation. However, recent data indicate that DNA methylation changes in repressed regions accumulate in every cell division, and thus, they can reflect the proliferative history of the cell. The evaluation of this epigenetic feature in cancer cells may provide information regarding the tumor cell biological evo...

Antileukemic Activity of 8-Chloro-Adenosine (8-Cl-Ado) Is Mediated By Mir-155 Degradation and ErbB3 Binding Protein (Ebp1)-Dependent p53 Activation: A Novel Therapeutic Approach for FLT3-ITD Acute ...
http://www.bloodjournal.org/content/132/Suppl_1/3938

Nov 21st, 2018 - AML patients (pts) carrying the fms-related tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) have a poor prognosis. Combination of chemotherapy with tyrosine kinase inhibitors (TKIs) has improved survival of these pts, but a large proportion of them still die of their disease. Nucleoside analogs (NAs) are the backbone of several upfront and salvage chemotherapy regimens for AML, inclu...

An Indirect Comparison between Bosutinib, Nilotinib and Dasatinib in First-Line Chronic Phase Chronic Myeloid Leukemia
http://www.bloodjournal.org/content/132/Suppl_1/1742

Nov 21st, 2018 - Introduction Several randomized controlled trials (RCTs) compare second generation tyrosine kinase inhibitors (TKIs) with imatinib (IM) for the first-line (1L) treatment of chronic phase chronic myeloid leukemia (CP-CML). However, an examination indicated cross-trial heterogeneity in terms of disease and patient characteristics (baseline risk score, age, trial region, and post-baseline IM dose ...

Glasdegib in Addition to Intensive or Non-Intensive Chemotherapy in Patients with Acute Myeloid Leukemia: Safety Analysis of Glasdegib 'On Target' Adverse Events
http://www.bloodjournal.org/content/132/Suppl_1/2732

Nov 21st, 2018 - Background: Novel agents are frequently added to standard acute myeloid leukemia (AML) treatment backbones yet it is unclear how much additional toxicity this introduces, with the potential for adverse events (AEs) to be caused by the backbone chemotherapy or the disease itself. Glasdegib (PF-04449913) is an investigational, oral small molecule inhibitor of the Hedgehog (Hh) pathway component S...

Anticoagulation Prophylaxis with Weight-Adjusted Enoxaparin Reduces Rates of Venous Thromboembolism in Patients with Acute Lymphoblastic Leukemia Receiving Asparaginase-Based Intensification Therapy
http://www.bloodjournal.org/content/132/Suppl_1/3974

Nov 21st, 2018 - Background Venous thromboembolism (VTE) is a well-known complication in adults receiving asparaginase (ASNase)-based intensification chemotherapy for acute lymphoblastic leukemia (ALL). The optimal preventative strategy is unclear. We previously reported high thrombosis rates during intensification without VTE prophylaxis. Our objective is to determine the effects of weight-adjusted enoxaparin ...

Global Transcriptome Profiling Identifies a Key Mir-185-PAK6 Axis That Promotes Survival of Leukemic Stem Cells and Drug-Insensitive Blasts in BCR-ABL+ Human Leukemia
http://www.bloodjournal.org/content/132/Suppl_1/931

Nov 21st, 2018 - Chronic myeloid leukemia (CML) stem/progenitor cells and BCR-ABL+ acute lymphoblastic leukemia (ALL) blast cells are insensitive to tyrosine kinase inhibitor (TKI) monotherapies. These cells rapidly generate therapy-resistant clones in vitro and in vivo and are often responsible for disease relapse. Therefore, identification of predictive biomarkers and novel treatments that target key molecula...

Efficacy and Safety of Generic Imatinib Compared to Glivec in Chronic Phase - Chronic Myeloid Leukemia - a Multicenter, Observational Study
http://www.bloodjournal.org/content/132/Suppl_1/46

Nov 21st, 2018 - Glivec was the first tyrosine kinase inhibitor (TKI) approved for chronic myeloid leukemia (CML) treatment and its efficacy has been demonstrated in a large number of trials. Generic formulations have been used recently as a more cost effective treatment, but there are few studies that have prospectively evaluated the efficacy and safety of these drugs.Aims: The present study aimed to evaluate ...