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Copy Number Monitoring from Tumor-Only Targeted Gene Sequencing in Hematological Malignancies
http://www.bloodjournal.org/content/132/Suppl_1/4086

Nov 21st, 2018 - The occurrence of copy number variation (CNV) observed in hematological malignancies could be up 20%~70%, variable in specific subtypes, but the available molecular diagnosis directed to the clinic are always limited among SNVs and Indels. In contrast, the copy number variation which cover broader genome region has not yet come to be implemented in clinical examination. Recently, the CNV in hem...

64cu-DOTA-Anti-CD33 PET-CT Imaging for Acute Myeloid Leukemia and Image-Guided Treatment
http://www.bloodjournal.org/content/132/Suppl_1/2747

Nov 21st, 2018 - Introduction: Acute myeloid leukemia (AML) is a highly aggressive form of leukemia that results a poor survival outcome. Currently, diagnosis and prognosis are based on invasive single-point bone marrow biopsies (iliac crest). Although non-invasive positron emission tomography (PET) imaging has been developed for almost all solid tumors and some hematological malignancies, there is currently no...

Critical Role of Jumonji Domain of JMJD1C in AML Leukemogenesis
http://www.bloodjournal.org/content/132/Suppl_1/2599

Nov 21st, 2018 - MLL-rearranged leukemias are found in 5-10% of adult leukemias and over 70% of infant leukemias and are associated with intermediate to poor prognosis. We have recently shown that JMJD1C, a Jumonji domain containing lysine demethylase (KDM), is important for leukemia stem cell (LSC) function in MLL-AF9 and HOXA9 leukemias but dispensable for normal hematopoietic stem cell function, therefore a ...

CXCR4 Has a CXCL12-Independent Essential Role in MLL-AF9 Driven Acute Myeloid Leukemia
http://www.bloodjournal.org/content/132/Suppl_1/774

Nov 21st, 2018 - Acute Myeloid Leukemia (AML) is a clonal hematological disorder associated with poor prognosis, and there is a strong need to develop new therapeutic strategies. AML is propagated by a small population of leukemic cells in the bone marrow with self-renewal capacity, a population termed leukemia stem cells (LSC). To identify in vivo dependencies of LSCs, we conducted a CRISPR/Cas9 drop-out scree...

Cytokine Gene Polymorphisms Are Associated with Disease Response to Blinatumomab in Patients with B-Cell Acute Lymphoblastic Leukemia
http://www.bloodjournal.org/content/132/Suppl_1/1549

Nov 21st, 2018 - Blinatumomab (BT), a CD19/CD3 bispecific T-cell engager (BiTE) antibody recently approved for treatment of relapsed/refractory acute lymphoblastic leukemia (r/r ALL), has resulted in a 40-50% complete response (CR)/CR with incomplete count recovery (CRi) rate and frequent cytokine release syndrome (CRS) events. While extent of disease burden has been identified as a key predictor of disease res...

A Leukemic Progression Model of Severe Congenital Neutropenia Uncovers a Novel Mechanism of AML Development Involving Elevated Inflammatory Responses, Mutation of CXXC4 and Decreased TET2 Levels
http://www.bloodjournal.org/content/132/Suppl_1/540

Nov 21st, 2018 - Introduction: Severe congenital neutropenia (SCN) patients receive life-long treatment with CSF3/G-CSF to alleviate neutropenia and have a high risk to develop MDS or AML. The appearance of hematopoietic clones with CSF3 receptor (CSF3R) mutations represents a first step in MDS/AML progression, which is followed by mutations in RUNX1 shortly before MDS/AML becomes clinically overt. How intracel...

Deep Molecular Response in Imatinib First-Line 418 Newly Diagnosed CP CML Patients.
http://www.bloodjournal.org/content/132/Suppl_1/3014

Nov 21st, 2018 - Introduction Deep molecular response (DMR) are now highly desirable goals in the treatment of CP-CML, especially in the front-line setting, because it can lead to a definitive treatment-free remission (TFR). However, such a goal is difficult to attain and does not concern the majority of patients (pts), but currently the precise number of pts able to access to TFR is unknown. Aims We aim to det...

Detection of Clinically Relevant Molecular Alterations in Chronic Lymphocytic Leukemia (CLL) By Nanopore Sequencing
http://www.bloodjournal.org/content/132/Suppl_1/1847

Nov 21st, 2018 - Introduction Chronic Lymphocytic Leukaemia (CLL) is the most prevalent leukaemia in the Western world and characterised by clinical heterogeneity. IgHV mutation status, mutations in the TP53 gene and deletions of the p-arm of chromosome 17 are currently used to predict an individual patient's response to therapy and give an indication as to their long-term prognosis. Current clinical guidelines...

A Personalized Prediction Model for Outcomes after Allogeneic Hematopoietic Stem Cell Transplant in Patients with Myelodysplastic Syndromes: On Behalf of the CIBMTR Chronic Leukemia Committee
http://www.bloodjournal.org/content/132/Suppl_1/206

Nov 21st, 2018 - Background Allogeneic hematopoietic cell transplantation (HCT) remains the only potentially curative option for myelodysplastic syndromes (MDS). Genetic alterations have an impact on outcomes after HCT in MDS (Lindsley C, et al, NEJM 2017). Given the significant risks of transplant-related mortality and relapse, identifying patients (pts) who may or may not benefit from HCT is clinically import...

Discovery and Development of MEDI7247, a Novel Pyrrolobenzodiazepine (PBD)-Based Antibody Drug Conjugate Targeting ASCT2, for Treating Hematological Cancers
http://www.bloodjournal.org/content/132/Suppl_1/4071

Nov 21st, 2018 - The neutral amino acid transporter, ASCT2, is frequently overexpressed in several cancers to sustain "glutamine addiction" of cancer cells. High expression of ASCT2 is often associated with poor disease prognosis. Immuno-histochemistry (IHC) on formalin-fixed paraffin embedded (FFPE) tissue samples revealed high prevalence of membranous ASCT2 expression in several hematological cancers, includi...

A Phase II Study of the Hyper-CVAD Regimen in Sequential Combination with Blinatumomab As Frontline Therapy for Adults with B-Cell Acute Lymphoblastic Leukemia (B-ALL)
http://www.bloodjournal.org/content/132/Suppl_1/32

Nov 21st, 2018 - Background Multi-agent combination chemotherapy regimens for the treatment of ALL are considered a cancer success story in the pediatric setting. For adults, the same magnitude of success has not been realized using similar strategies. These regimens produce high complete remission (CR) rates of 80-90% but the cure rates are 40-50%. The incorporation of targeted agents (tyrosine kinase inhibito...

Discrepant Mutational Composition between Myeloid Sarcoma and Bone Marrow Leukemia Revealed through Targeted Next Generation Sequencing
http://www.bloodjournal.org/content/132/Suppl_1/1395

Nov 21st, 2018 - Introduction: Myeloid sarcoma (MS) is the involvement of acute myeloid leukemia (AML) cells in extramedullary tissues, whose mechanism remains to be further elucidated. How MS affects AML prognosis at a molecular level is also an open question. This unexplained tropism of leukemic blasts to extramedullary tissues is likely caused by the combination of genetic and epigenetic aberrations. Our stu...

A Scoring System to Predict the Risk of Atrial Fibrillation in Chronic Lymphocytic Leukemia and Its Validation in a Cohort of Ibrutinib-Treated Patients
http://www.bloodjournal.org/content/132/Suppl_1/3118

Nov 21st, 2018 - BACKGROUD. The B-cell receptor inhibitor ibrutinib has significantly improved treatment and overall management of chronic lymphocytic leukemia (CLL). Although several data derived from clinical trials suggest that ibrutinib increases the risk of atrial fibrillation (AF), the incidence of AF in a real-life cohort of CLL patients is unknown. Furthermore, it would be clinically relevant to identif...

A Tumor Suppressor Role for Bank1 in B-Cell Precursor Acute Lymphoblastic Leukemia
http://www.bloodjournal.org/content/132/Suppl_1/1333

Nov 21st, 2018 - Introduction: Since the implementation of next generation sequencing techniques, inherited mutations in malignancy-associated susceptibility genes have become of major interest, to identify high-risk individuals, even before an actual disease onset. One challenge in this regard is that germline susceptibility variants often display incomplete or reduced penetrance, which can be influenced by ge...

Aberrant Splicing of KMT2A As a Potential Molecular MRD Marker in Cytogenetically-Normal AML
http://www.bloodjournal.org/content/132/Suppl_1/1504

Nov 21st, 2018 - Cytogenetically normal acute myeloid leukaemia (CN-AML) accounts for approximately 25%-30% of paediatric AML cases and carries a high risk of relapse. Minimal residual disease (MRD) is an essential factor in predicting relapse in acute leukaemia but is difficult to track for many CN-AML patients, due to the lack of a distinct and stable molecular marker. Consequently, new biomarkers are urgentl...

Absence of NKG2D Ligands Defines Human Acute Myeloid Leukaemia Stem Cells and Mediates Their Immune Evasion
http://www.bloodjournal.org/content/132/Suppl_1/769

Nov 21st, 2018 - Patients with acute myeloid leukaemia (AML) often achieve remission but subsequently die of relapse driven by chemotherapy resistant leukemic stem cells (LSCs). To initiate and maintain cancer, LSCs must also escape immunosurveillance. However, in vivo studies on human LSCs largely disregard lymphocyte mediated anti-tumor immunity due to the use of immunocompromised mice. Here we investigate th...

Donor Cell Leukemia: The Role of Recipient Microenvironment
http://www.bloodjournal.org/content/132/Suppl_1/3853

Nov 21st, 2018 - Acute myeloid leukemia (AML) is one of the extreme outcomes of age-related clonal hematopoiesis (ARCH). In recent years, data on differences between pre-AML and ARCH have emerged. However, it is still enigmatic why ARCH is prevalent in the general aging population, whereas only very few individuals eventually develop AML. Whether ARCH is solely related to abnormal hematopoiesis or originates fr...

Accounting for the Unique Molecular Landscape of Pediatric Malignancies Improves Target-Agent Pair Identification for Pediatric Precision Oncology
http://www.bloodjournal.org/content/132/Suppl_1/2829

Nov 21st, 2018 - Precision medicine has significant potential to improve therapy options for patients who have exhausted treatment options for their relapsed or refractory cancers. Next-generation sequencing has enabled the detection of genetic abnormalities in individual tumours that bestow sensitivity to selective agents targeting these dysregulated cellular pathways. Several programs have recently launched t...

Dosing Patterns of Dasatinib Use in Simplicity, an Observational Study in Chronic Phase Chronic Myeloid Leukemia (CP-CML) Patients (pts) in Routine Clinical Practice
http://www.bloodjournal.org/content/132/Suppl_1/1730

Nov 21st, 2018 - Introduction: Treatment dosing patterns have not been well documented among dasatinib-treated CP-CML pts outside of clinical trials. SIMPLICITY (NCT01244750) is an ongoing observational study of CP-CML adult pts in routine clinical practice receiving tyrosine kinase inhibitors (TKI) since 2010 in the US and Europe, exploring TKI use and management patterns in clinical practice. This analysis re...

Activation of CRLF2/IL7RA Signaling in Normal Human Cord Blood Hematopoietic Progenitors Induces Philadelphia-like B-Cell Precursor Pre-Leukemia and Leukemia In Vivo
http://www.bloodjournal.org/content/132/Suppl_1/566

Nov 21st, 2018 - Philadelphia-like (Ph-like) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a subgroup of BCP-ALL with an expression pattern similar to BCR-ABL+ BCP-ALL that is associated with poor prognosis. Aberrant expression of CRLF2 in BCP-ALL constitutes the majority of Ph-like BCP-ALL cases. CRLF2 is a receptor subunit that together with the IL7RA subunit comprises the receptor of the proinfl...