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ATG2B/Gskip in De Novo Acute Myeloid Leukemia (AML): High Prevalence of Germline Predisposition in French West Indies and Potential Role of Overexpression in Acquired AML
http://www.bloodjournal.org/content/132/Suppl_1/1482

Nov 21st, 2018 - In 2015, a germline copy number variation of chromosome 14 (CNVdup14) including ATG2B and GSKIP genes was described as a predisposition genetic factor responsible of familial myeloproliferative neoplasms from French West Indies (Saliba et al, Nat Gen 2015), frequently progressing to AML. In this study, we looked at the presence of this CNVdup14 in a cohort of Caribbean islands patients (pts) wi...

BET Inhibitors Potentiate Activation of p53 and Killing of AML By MDM2 Inhibitors — a Candidate Combination Therapy
http://www.bloodjournal.org/content/132/Suppl_1/3912

Nov 21st, 2018 - In 2016, there will be approximately 19,950 new cases of Acute Myeloid Leukaemia (AML) in the United States. After diagnosis, five-year survival is currently ~26%, with available therapeutic approaches. Therefore, there remains a critical requirement for novel therapies for AML. Bromodomain and extra-terminal domain inhibitors (BETi) are emerging as exciting therapeutic agents for haematopoieti...

B-Cell Receptor Signaling Drives Glycolysis in Chronic Lymphocytic Leukemia Cells
http://www.bloodjournal.org/content/132/Suppl_1/3121

Nov 21st, 2018 - A key feature of tumor cell energetics is preferential metabolism of glucose to lactate even in the presence of oxygen (aerobic glycolysis). While this is an inefficient way of producing energy, it enables cancer cells to use glucose to generate biomass to support cellular proliferation. It is unclear whether this process is playing a role in the pathogenesis of chronic lymphocytic leukemia (CL...

Bone Marrow Hematopoietic Dysfunction in Untreated Chronic Lymphocytic Leukemia Is Partially Mediated By Exposure to Constituents of the Leukemic Microenvironment
http://www.bloodjournal.org/content/132/Suppl_1/3132

Nov 21st, 2018 - Peripheral immune dysfunction in B-Chronic Lymphocytic Leukemia (CLL) is well-studied and likely relates to the incidence of serious recurrent infections and second malignancies that plague CLL patients. However, the current paradigms of known immune abnormalities are not able to consistently explain these complications and it is not easy to correct CLL patient immune status. Here, we expand on...

Blinatumomab in Combination with Immune Checkpoint Inhibitors of PD-1 and CTLA-4 in Adult Patients with Relapsed/Refractory (R/R) CD19 Positive B-Cell Acute Lymphoblastic Leukemia (ALL): Preliminar...
http://www.bloodjournal.org/content/132/Suppl_1/557

Nov 21st, 2018 - Background: Blinatumomab, a CD19/CD3 bispecific T cell engager antibody construct, leads to improved outcomes in patients with R/R CD19+ ALL compared to standard chemotherapy. However, most adults fail to achieve complete remission (CR) with blinatumomab, and the median duration of remission is only 7.3 months. Preclinical studies have shown significantly increased PD-L1 expression on leukemic ...

BST-236, a Novel Cytarabine Prodrug, Is Safer and As Effective As Cytarabine in In Vivo Leukemia Models
http://www.bloodjournal.org/content/132/Suppl_1/1451

Nov 21st, 2018 - Introduction: Acute myeloid leukemia (AML) is associated with poor outcomes in older and medically unfit patients, largely due to the severe toxicity associated with cytarabine treatment, which precludes the administration of effective cytarabine doses. BST-236 is a prodrug of cytarabine, inactive in its prodrug form and designed to deliver cytarabine to leukemia cells with reduced systemic tox...

BRCA1/2 Containing Complex 3 (BRCC36) Is Recurrently Mutated in AML with t(8;21) and Associated with Increased Sensitivity to Chemotherapy through Impairment of the DNA Damage Repair Pathway
http://www.bloodjournal.org/content/132/Suppl_1/1487

Nov 21st, 2018 - Introduction BRCA1/BRCA2-containing complex 3 (BRCC36) is a Lys63-specific deubiquitinating enzyme (DUB) involved in DNA damage repair. Mutations in BRCC36 have been identified in 2-3% of patients with myelodysplastic syndromes (MDS) and secondary AML (sAML). The role of BRCC36 mutations in de novo AML and their impact on DNA damage-inducing cytotoxic chemotherapy sensitivity is not clear. Aim ...

Catecholamine Exposure Accelerates In Vivo Leukemogenesis in Acute Myeloid Leukemia Patient Derived Xenografts
http://www.bloodjournal.org/content/132/Suppl_1/1475

Nov 21st, 2018 - Mouse xenografts are routinely used for in vivo studies on human acute myeloid leukemia (AML) cells. However, a significant proportion of primary AML samples (~50-60% of cases) are not able to repopulate mice, or respectively require a particularly long time (up to 9 months) to show detectable engraftment in such models. Here we report that changing the transplantation time-point from day (5:00...

Cardiovascular Mortality Among CML Patients in the Pre-TKI and TKI Eras: A SEER Analysis 1992-2004
http://www.bloodjournal.org/content/132/Suppl_1/1737

Nov 21st, 2018 - Background: Since the US Food and Drug Administration (FDA) approved the first BCR-ABL1-targeted tyrosine kinase inhibitor (TKI) imatinib in 2002 as the first line therapy1, chronic phase chronic myeloid leukemia (CML-CP), once a uniformly fatal disease, now has become a disease that is controlled in >90% patients2. Conventional treatment for CML before TKIs included hydroxyurea, interferon alp...

CD79a Is Associated with Central Nervous System Infiltration of Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia
http://www.bloodjournal.org/content/132/Suppl_1/386

Nov 21st, 2018 - Despite the advances in the treatment of pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), infiltration of the central nervous system (CNS) remains a clinical challenge. Certain cytogenetic subtypes such as E2A-PBX1-and BCR-ABL-positive BCP-ALL confer a higher risk for CNS involvement initially and for CNS relapse. Novel strategies to predict CNS and to eradicate leukemic cells...

CD37 Expression in Acute Myeloid Leukemia Provides New Target for Directed Therapy
http://www.bloodjournal.org/content/132/Suppl_1/4056

Nov 21st, 2018 - Background: Acute myeloid leukemia (AML) is a disease for which there is an urgent need for therapy that is more effective and less toxic. Antibody based therapy has been of limited success due to both the lack of consistent immunophenotype in AML as well as the overlap with normal hematopoetic stem cells (HSCs). CD37 is a tetraspanin best characterized for its role in B-cell development and im...

Characteristic Amino Acid and Energy Metabolism in AML Stem Cells As Revealed By Quantitative Multiplex Proteomics
http://www.bloodjournal.org/content/132/Suppl_1/2780

Nov 21st, 2018 - Acute Myeloid Leukemia (AML) is a rapidly progressing hematologic malignancy characterized by the accumulation of clonal myeloid progenitor cells arrested in their ability to differentiate into mature blood cells. While classic chemotherapy regimens lead to remission in the majority of patients, relapse rates are very high. Relapse and also refractoriness are caused by the hierarchical organiza...

Characteristics, Treatment Patterns and Outcomes Among Newly Diagnosed Patients (pts) with Acute Myeloid Leukemia (AML) Who Present with Hyperleukocytosis: Findings from a Large International Patie...
http://www.bloodjournal.org/content/132/Suppl_1/4040

Nov 21st, 2018 - Introduction: Pts with AML often present with hyperleukocytosis, defined with a white blood cell count (WBC) of >50 or >100 × 109/L. Hyperleukocytosis is associated with higher rates of complications and death especially when associated with clinical leukostasis. There are no clear guidelines outlining the best cytoreductive strategy and the use of leukapheresis is based on institutional practi...

Characteristics and Outcome of Older Patients with Acute Promyelocytic Leukemia Front-Line Treated with or without Arsenic Trioxide — an International Collaborative Study
http://www.bloodjournal.org/content/132/Suppl_1/80

Nov 21st, 2018 - Background: Characteristics and outcome of older patients (pts) with acute promyelocytic leukemia (APL) are unclear due to lack of clinical data. Aims: To describe a large series of older APL pts and compare outcome according to treatment strategy. Methods: We retrospectively studied 475 APL pts (median age, 73.8 yrs; range, 70-90.3 yrs), treated between 1990 and 2018 within four study groups/i...

Chemoimmunotherapy with Inotuzumab Ozogamicin Combined with Mini-Hyper-CVD, with or without Blinatumomab, for Newly Diagnosed Older Patients with Philadelphia Chromosome-Negative Acute Lymphoblasti...
http://www.bloodjournal.org/content/132/Suppl_1/36

Nov 21st, 2018 - Background: Both the anti-CD22 antibody-drug conjugate inotuzumab ozogamicin (INO) and the CD3-CD19 bispecific T-cell engager blinatumomab have single-agent activity in relapsed or refractory acute lymphoblastic leukemia (ALL). We previously reported the promising efficacy and survival of INO in combination with low-intensity mini-hyper-CVD chemotherapy in older adults with newly diagnosed ALL ...

Checkpoint Inhibitors Augment CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy in Relapsed B-Cell Acute Lymphoblastic Leukemia
http://www.bloodjournal.org/content/132/Suppl_1/556

Nov 21st, 2018 - CAR T cell therapy in relapsed B-ALL can result in complete response (CR) rates of 80-90%, but relapse-free survival declines to 60% within the first 12-months due to both CD19-positive and negative relapses. CD19-positive relapses that occur during this time are largely due to early CAR T cell loss. We hypothesize that inhibiting the PD-1:PD-L1 (programmed cell death 1) checkpoint axis may dec...

Chloroquine Derivative Lys05 Overcomes Hypoxia-Induced Chemoresistance in Acute Myeloid Leukemia through Metabolic Disruption
http://www.bloodjournal.org/content/132/Suppl_1/3948

Nov 21st, 2018 - Background: Despite initial responses to standard chemotherapy, most patients with acute myeloid leukemia (AML) relapse and have poor prognoses after subsequent therapy. The hypoxic bone marrow (BM) microenvironment is hypothesized to contribute to clinical resistance through the sheltering of AML blasts and leukemia stem cells (LSCs), allowing them to evade chemotherapy and reinitiate the dise...

Chronic Myeloid Leukemia Italian Multicenter Observational Study (CML-IT-MOS): Clinical Characteristics of Chronic Myeloid Leukemia (CML) Patients Treated in Real-Life between 2012 and 2016 in 66 I...
http://www.bloodjournal.org/content/132/Suppl_1/45

Nov 21st, 2018 - Background: The advent of Tyrosine Kinase Inhibitors (TKI) totally changed the outcome of patients affected by Chronic Myeloid Leukemia (CML). Most of informations about the clinical characteristics of CML patients are based on data derived from clinical trials, that often exclude patients not fitting with strict inclusion criteria. In real life may be important to know the characteristics of t...

Cirmtuzumab Inhibits Non-Canonical Wnt Signaling without Enhancing Canonical Wnt/β-Catenin Signaling in Chronic Lymphocytic Leukemia
http://www.bloodjournal.org/content/132/Suppl_1/2652

Nov 21st, 2018 - ROR1 is a receptor tyrosine kinase-like orphan receptor for Wnt5a that is expressed by cells during embryogenesis and by the neoplastic cells of a variety of cancers, including chronic lymphocytic leukemia (CLL). ROR1 can induce activation of β-catenin-independent non-canonical Wnt-signaling. Studies reveal a cross-talk between the non-canonical Wnt-signaling pathway and the β-catenin-dependent...

Clinical Characteristics and Outcomes of 82 Patients with Mixed-Phenotype Acute Leukemia
http://www.bloodjournal.org/content/132/Suppl_1/1124

Nov 21st, 2018 - Objectives: Mixed-phenotype acute leukemia(MPAL) is a rare disease and comprises 2% to 5% of all acute leukemia. Outcomes for MPAL are worse than both acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).The complex phenotype exhibited by this type of leukemia resulted in a myriad of treatment approaches.In our study, we retrospective analysis 82 patients in clinical trail, treat...