Addressing a Pre-Clinical Pipeline Gap: Development of the Pediatric Acute Myeloid Leukemia Patient-Derived Xenograft Program at Texas Children’s Hospital at Baylor College of Medicine
Alexandra M. Stevens,
Maci Terrell,
Raushan Rashid,
Kevin E. Fisher,
Andrea N. Marcogliese,
Amos Gaikwad,
Pulivarthi Rao,
Chelsea Vrana,
Michael Krueger,
Michael Loken,
Andrew J. Menssen,
Jacqueline A. Cook,
Noah Keogh,
Michelle Alozie,
Hailey Oviedo,
Alan K. Gonzalez,
Tamilini Ilangovan,
Julia Kim,
Sohani Sandhu,
Michele S. Redell
Affiliations
Alexandra M. Stevens
Section of Hematology/Oncology, Department of Pediatrics, Texas Children’s Cancer and Hematology Center, Baylor College of Medicine, 1102 Bates St, Suite 750, Houston, TX 77030, USA
Maci Terrell
Section of Hematology/Oncology, Department of Pediatrics, Texas Children’s Cancer and Hematology Center, Baylor College of Medicine, 1102 Bates St, Suite 750, Houston, TX 77030, USA
Raushan Rashid
Section of Hematology/Oncology, Department of Pediatrics, Texas Children’s Cancer and Hematology Center, Baylor College of Medicine, 1102 Bates St, Suite 750, Houston, TX 77030, USA
Kevin E. Fisher
Department of Pathology & Immunology, Baylor College of Medicine, Genomic Medicine Division, Texas Children’s Hospital, Houston, TX 77030, USA
Andrea N. Marcogliese
Department of Pathology & Immunology, Baylor College of Medicine, Laboratory Medicine Division, Texas Children’s Hospital, Houston, TX 77030, USA
Amos Gaikwad
Section of Hematology/Oncology, Department of Pediatrics, Texas Children’s Cancer and Hematology Center, Baylor College of Medicine, 1102 Bates St, Suite 750, Houston, TX 77030, USA
Pulivarthi Rao
Section of Hematology/Oncology, Department of Pediatrics, Texas Children’s Cancer and Hematology Center, Baylor College of Medicine, 1102 Bates St, Suite 750, Houston, TX 77030, USA
Chelsea Vrana
Section of Hematology/Oncology, Department of Pediatrics, Texas Children’s Cancer and Hematology Center, Baylor College of Medicine, 1102 Bates St, Suite 750, Houston, TX 77030, USA
Michael Krueger
Section of Hematology/Oncology, Department of Pediatrics, Texas Children’s Cancer and Hematology Center, Baylor College of Medicine, 1102 Bates St, Suite 750, Houston, TX 77030, USA
Michael Loken
Hematologics, Seattle, WA 98121, USA
Andrew J. Menssen
Hematologics, Seattle, WA 98121, USA
Jacqueline A. Cook
Hematologics, Seattle, WA 98121, USA
Noah Keogh
Section of Hematology/Oncology, Department of Pediatrics, Texas Children’s Cancer and Hematology Center, Baylor College of Medicine, 1102 Bates St, Suite 750, Houston, TX 77030, USA
Michelle Alozie
Section of Hematology/Oncology, Department of Pediatrics, Texas Children’s Cancer and Hematology Center, Baylor College of Medicine, 1102 Bates St, Suite 750, Houston, TX 77030, USA
Hailey Oviedo
Section of Hematology/Oncology, Department of Pediatrics, Texas Children’s Cancer and Hematology Center, Baylor College of Medicine, 1102 Bates St, Suite 750, Houston, TX 77030, USA
Alan K. Gonzalez
Section of Hematology/Oncology, Department of Pediatrics, Texas Children’s Cancer and Hematology Center, Baylor College of Medicine, 1102 Bates St, Suite 750, Houston, TX 77030, USA
Tamilini Ilangovan
Section of Hematology/Oncology, Department of Pediatrics, Texas Children’s Cancer and Hematology Center, Baylor College of Medicine, 1102 Bates St, Suite 750, Houston, TX 77030, USA
Julia Kim
Section of Hematology/Oncology, Department of Pediatrics, Texas Children’s Cancer and Hematology Center, Baylor College of Medicine, 1102 Bates St, Suite 750, Houston, TX 77030, USA
Sohani Sandhu
Section of Hematology/Oncology, Department of Pediatrics, Texas Children’s Cancer and Hematology Center, Baylor College of Medicine, 1102 Bates St, Suite 750, Houston, TX 77030, USA
Michele S. Redell
Section of Hematology/Oncology, Department of Pediatrics, Texas Children’s Cancer and Hematology Center, Baylor College of Medicine, 1102 Bates St, Suite 750, Houston, TX 77030, USA
The survival rate of pediatric acute myeloid leukemia (pAML) is currently around 60%. While survival has slowly increased over the past few decades, the development of novel agents likely to further improve survival for this heterogeneous patient population has been limited by gaps in the pAML pre-clinical pipeline. One of the major hurdles in evaluating new agents for pAML is the lack of pAML patient-derived xenograft (PDX) models. Unlike solid tumors and other types of leukemias, AML is notoriously hard to establish in mouse models, likely due in part to the need for specific human microenvironment elements. Our laboratory at TCH/BCM addressed this gap by establishing a systematic PDX workflow, leveraging advanced immunodeficient hosts and capitalizing on our high volume of pAML patients and close coordination between labs and clinical sections. Patients treated at TCH are offered the chance to participate in specimen banking protocols that allow blood and bone marrow collection as well as the collection of relevant clinical data. All patients who consent and have samples available are trialed for PDX development. In addition, samples from the Children’s Oncology Group (COG) are also trialed for PDX generation. Serially transplanting PDX models are validated using short tandem repeat (STR) and characterized using both targeted DNA/RNA next generation sequencing and RNAseq. As of March 2023, this systematic approach has resulted in 26 serially transplanting models. Models have been shared with requesting labs to facilitate external pAML pre-clinical studies. Available PDX models can be located through the BCM PDX Portal. We expect our growing PDX resource to make a significant contribution to expediting the testing of promising novel therapeutics for pAML.