57th ASH Annual Meeting and Exposition (December 5-8, 2015): 631. Chronic Myeloid Leukemia: Biology and Pathophysiology, excluding Therapy: CML – Mechanisms of Disease Progression and Leukemic Stem Cell Persistence

Chronic Myeloid Leukemia: Biology and Pathophysiology, excluding Therapy Oral and Poster Abstracts
Oral

W340, Level 3 (Orange County Convention Center)

Moderators:

Xiaoyan Jiang, MD, PhD, BC Cancer Agency and University of British Columbia and Simona Soverini, Bologna University School of Medicine

Disclosures:

No relevant conflicts of interest to declare.

7:30 AM

Single Cell Whole Transcriptome Analysis Reveals Distinct Molecular Signatures of Therapy-Resistant Chronic Myeloid Leukemia Stem Cells

Alice Giustacchini^1,2^*, Supat Thongjuea^1,2^*, Petter S. Woll, Ph.D.^1,2^*, Paul Sopp¹^*, Ana Duenas Perez²^*, Nikolaos Barkas^1,2^*, Christopher Booth^1,2^*, Ruggiero Norfo^1,2^*, Sally-Ann Clark^1,2^*, Lauren Jamieson^2,3^*, Sten Eirik Jacobsen, MD PhD^2,3^* and Adam Mead^3,4,5^*

¹MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom
²Haemopoietic Stem Cell Laboratory, Weatherall Institute for Molecular Medicine, University of Oxford, Oxford, United Kingdom
³MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom
⁴Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom
⁵NIHR Biomedical Research Centre, Churchill Hospital, Oxford, United Kingdom

7:45 AM

MS4A3 Improves Imatinib Response and Survival in BCR-ABL1 Primary TKI Resistance and in Blastic Transformation of Chronic Myeloid Leukemia

Anna M. Eiring, PhD¹, Jamshid S. Khorashad, MD, PhD¹^*, Anupriya Agarwal, PhD², Clinton C. Mason, PhD¹^*, Fan Yu, MD¹^*, Hannah M. Redwine¹^*, Amber D. Bowler¹^*, Kevin C. Gantz¹^*, Kimberly R. Reynolds, MS¹^*, Phillip M. Clair, MS¹^*, David J. Anderson, MBA¹^*, Srinivas K Tantravahi¹, Shannon K. McWeeney, PhD³^*, Brian J. Druker, MD⁴, Derek L. Stirewalt, MD⁵, Vivian G. Oehler, MD⁶, Thomas O'Hare, PhD⁷ and Michael W. Deininger⁸

¹Huntsman Cancer Institute, The University of Utah, Salt Lake City, UT
²Knight Cancer Institute, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR
³Department of Bioinformatics and Computational Biology, Oregon Health & Science University, Portland, OR
⁴Knight Cancer Institute, Oregon Health & Science University, Portland, OR
⁵Fred Hutchinson Cancer Research Ctr., Seattle, WA
⁶Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
⁷Huntsman Cancer Institute, The University of Utah, Division of Hematology and Hematologic Malignancies, Salt Lake City, UT
⁸Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute, The University of Utah, Salt Lake City, UT

8:00 AM

A Novel TNF-Alpha Antibody Based Therapeutic Approach to Target Leukemic Stem Cells in Bcr-Abl Disease

Oliver Herrmann, Msc¹^*, Claudia Schubert, Msc¹^*, Tom Luedde, MD, PhD²^*, Till Braunschweig, MD³^*, Steffen Koschmieder, MD⁴, Tim H Brümmendorf, MD¹^* and Mirle Schemionek, PhD¹^*

¹Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, University Hospital RWTH Aachen, Aachen, Germany
²Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
³Department of Pathology, University Hospital RWTH Aachen, Aachen, Germany
⁴RWTH Aachen University Hospital, Aachen, Germany

8:15 AM

Beclin-1 Phosphorylation By BCR-ABL Is Crucial for CML Leukemogenesis By Suppression of Autophagy

Chuanjiang Yu, M.S.¹^*, Sivahari Prasad Gorantla, Ph.D.¹^*, Tony Mueller, M.S.¹^*, Lena Lippert¹^*, Zhenyu Yue, Ph.D.²^*, Robert Zeiser, MD¹, Tobias Huber, M.D.³^*, Justus Duyster, MD⁴^* and Anna Lena Illert, M.D.¹^*

¹Department of Hematology, Oncology and Stem Cell Transplantation, University Medical Center Freiburg, Freiburg, Germany
²Departments of Neurology and Neuroscience, Friedman Brain Institute, Mount Sinai School of Medicine, New York
³Renal Division, University Medical Center Freiburg, Freiburg, Germany
⁴Department of Hematology, Oncology and Stem Cell Transplantation, University of Freiburg Medical Center, Freiburg, Germany

8:30 AM

Identification of TKI-Sensitive Point Mutations That Activate c-ABL Kinase Activity and Transformation Potential and Confer in Vitro Resistance to the Allosteric ABL Inhibitor GNF-5

Bianca J Lee, BA¹ and Neil P. Shah²

¹Department of Medicine, University of California, San Francisco, CA
²Department of Medicine, University of California at San Francisco, San Francisco, CA

8:45 AM

Chronic Myeloid Leukemia Patients with Deep Molecular Responses to Tyrosine Kinase Inhibitors Have Increased Effector Natural Killer and Cytotoxic T Cell Immune Responses to Leukaemia-Associated Antigens and Concomitant Reduced Immune Suppressors

Amy Hughes, B.Sc (hons), PhD¹^*, Carine Tang, B.Sc (hons), PhD²^*, Jade Clarson, B.Sc²^*, Ljiljana Vidovic, Animal Sc (hons)²^*, Timothy P. Hughes, MD, MBBS, FRACP, FRCPA³ and Agnes S Yong, MD, PhD¹

¹Department of Haematology - SA Pathology, School of Medicine - University of Adelaide, Adelaide, Australia
²Department of Haematology - SA Pathology, Adelaide, Australia
³SA Pathology and South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia

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^*signifies non-member of ASH

631.O2.6 631. Chronic Myeloid Leukemia: Biology and Pathophysiology, excluding Therapy: CML – Mechanisms of Disease Progression and Leukemic Stem Cell Persistence