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Celebrating one year of Blood Cancer Discovery!

July 2021
Read the July issue!
Editorial
Read: Blood Cancer Discovery Turns One, Riccardo Dalla-Favera and Kenneth C. Anderson
In the Spotlight
Read— Genomics, Transcriptomics, and Minimal Residual Disease Detection: The Winning Team to Guide Treatment of Acute Lymphoblastic Leukemia, Heidi Segers and Jan Cools
In the Spotlight
Read: Finding the Optimal Partner to Pair with Bispecific Antibody Therapy for Multiple Myeloma, Cedric Louvet, Omar Nadeem and Eric L. Smith
In the Spotlight
PML/RARα Destabilization by Hyperthermia: A New Model for Oncogenic Fusion Protein Degradation?, Hsin Chieh Wu, Domitille Rérolle and Hugues de Thé

From the Current Issue

Research Articles | Free Article

Tumor Burden Limits Bispecific Antibody Efficacy through T-cell Exhaustion Averted by Concurrent Cytotoxic Therapy

Erin W. Meermeier, Seth J. Welsh, Meaghen E. Sharik, Megan T. Du, Victoria M. Garbitt, Daniel L. Riggs, Chang-Xin Shi, Caleb K. Stein, Marco Bergsagel, Bryant Chau, Matthew L. Wheeler, Natalie Bezman, Feng Wang, Pavel Strop, P. Leif Bergsagel and Marta Chesi

Blood Cancer Discov July 1 2021 2 (4) 354-369; DOI:10.1158/2643-3230.BCD-21-0038

Bispecific antibody response in immunocompetent mice with high myeloma burden is transient due to ensuing T-cell exhaustion. Cyclophosphamide pretreatment prevents the exhaustion, enabling complete and durable bispecific antibody responses in animals with advanced disease.
Research Articles | Free Article

Clinical Significance of Novel Subtypes of Acute Lymphoblastic Leukemia in the Context of Minimal Residual Disease–Directed Therapy

Sima Jeha, John Choi, Kathryn G. Roberts, Deqing Pei, Elaine Coustan-Smith, Hiroto Inaba, Jeffrey E. Rubnitz, Raul C. Ribeiro, Tanja A. Gruber, Susana C. Raimondi, Seth E. Karol, Chunxu Qu, Samuel W. Brady, Zhaohui Gu, Jun J. Yang, Cheng Cheng, James R. Downing, Williams E. Evans, Mary V. Relling, Dario Campana, Charles G. Mullighan and Ching-Hon Pui

Blood Cancer Discov July 1 2021 2 (4) 326-337; DOI:10.1158/2643-3230.BCD-20-0229

Combining minimal residual disease monitoring with genome analysis demonstrates high-precision risk assessment in newly identified subtypes of pediatric ALL.
Review | Free Article

Determinants of Response and Mechanisms of Resistance of CAR T-cell Therapy in Multiple Myeloma

Niels W.C.J. van de Donk, Maria Themeli and Saad Z. Usmani

Blood Cancer Discov July 1 2021 2 (4) 302-318; DOI:10.1158/2643-3230.BCD-20-0227
Research Articles | Free Article

Lysine Demethylase 5A Is Required for MYC-Driven Transcription in Multiple Myeloma

Hiroto Ohguchi, Paul M.C. Park, Tingjian Wang, Berkley E. Gryder, Daisuke Ogiya, Keiji Kurata, Xiaofeng Zhang, Deyao Li, Chengkui Pei, Takeshi Masuda, Catrine Johansson, Virangika K. Wimalasena, Yong Kim, Shinjiro Hino, Shingo Usuki, Yawara Kawano, Mehmet K. Samur, Yu-Tzu Tai, Nikhil C. Munshi, Masao Matsuoka, Sumio Ohtsuki, Mitsuyoshi Nakao, Takashi Minami, Shannon Lauberth, Javed Khan, Udo Oppermann, Adam D. Durbin, Kenneth C. Anderson, Teru Hideshima and Jun Qi

Blood Cancer Discov July 1 2021 2 (4) 370-387; DOI:10.1158/2643-3230.BCD-20-0108

KDM5A is required for transcription elongation of Myc target genes in myeloma, and a small-molecule selective inhibitor shows activity in myeloma models.
Research Articles | Free Article

Hyperthermia Selectively Destabilizes Oncogenic Fusion Proteins

Yasen Maimaitiyiming, Qian Qian Wang, Chang Yang, Yasumitsu Ogra, Yinjun Lou, Clayton A. Smith, Liaqat Hussain, Yi Ming Shao, Jiebo Lin, Jinfeng Liu, Lingfang Wang, Yong Zhu, Haiyan Lou, Yuan Huang, Xiaoxia Li, Kao-Jung Chang, Hao Chen, Hongyan Li, Ying Huang, Eric Tse, Jie Sun, Na Bu, Shih-Hwa Chiou, Yan Fang Zhang, Hao Ying Hua, Li Ya Ma, Ping Huang, Ming Hua Ge, Feng-Lin Cao, Xiaodong Cheng, Hongzhe Sun, Jin Zhou, Vasilis Vasliou, Pengfei Xu, Jie Jin, Mikael Bjorklund, Hong-Hu Zhu, Chih-Hung Hsu and Hua Naranmandura

Blood Cancer Discov July 1 2021 2 (4) 388-401; DOI:10.1158/2643-3230.BCD-20-0188

PML-RARα and other fusion oncoproteins are heat unstable, and prone to aggregation and degradation in hyperthermia. Proof-of-principle patient cases illustrate how this vulnerability may be potentially exploited for therapy of refractory acute promyelocytic leukemia.
Research Articles | Free Article

ROBO1 Promotes Homing, Dissemination, and Survival of Multiple Myeloma within the Bone Marrow Microenvironment

Giada Bianchi, Peter G. Czarnecki, Matthew Ho, Aldo M. Roccaro, Antonio Sacco, Yawara Kawano, Annamaria Gullà, Anil Aktas Samur, Tianzeng Chen, Kenneth Wen, Yu-Tzu Tai, Maria Moscvin, Xinchen Wu, Gulden Camci-Unal, Matteo C. Da Vià, Niccolo' Bolli, Tomasz Sewastianik, Ruben D. Carrasco, Irene M. Ghobrial and Kenneth C. Anderson

Blood Cancer Discov July 1 2021 2 (4) 338-353; DOI:10.1158/2643-3230.BCD-20-0164

ROBO1 mediates multiple myeloma cell–intrinsic growth, as well as adhesion to stromal cells, homing, and engraftment in the bone marrow.
Research Brief | Free Article

Personalized Single-Cell Proteogenomics to Distinguish Acute Myeloid Leukemia from Nonmalignant Clonal Hematopoiesis

Laura W. Dillon, Jack Ghannam, Chidera Nosiri, Gege Gui, Meghali Goswami, Katherine R. Calvo, Katherine E. Lindblad, Karolyn A. Oetjen, Matthew D. Wilkerson, Anthony R. Soltis, Gauthaman Sukumar, Clifton L. Dalgard, Julie Thompson, Janet Valdez, Christin B. DeStefano, Catherine Lai, Adam Sciambi, Robert Durruthy-Durruthy, Aaron Llanso, Saurabh Gulati, Shu Wang, Aik Ooi, Pradeep K. Dagur, J. Philip McCoy, Patrick Burr, Yuesheng Li and Christopher S. Hourigan

Blood Cancer Discov July 1 2021 2 (4) 319-325; DOI:10.1158/2643-3230.BCD-21-0046

Leukemia and nonmalignant clonal hematopoiesis (CH) are indistinguishable by bulk sequencing assays. Here, DNA probes tailored to detect patient-specific oncogenic lesions are combined with multiplex immunophenotyping to definitively resolve leukemia and CH at a single-cell level.