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
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-c...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/12/2/394 |
| _version_ | 1797298849172160512 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Alexandra M. Stevens |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T22:41:00Z |
| format | Article |
| id | doaj.art-c34eed7c9c8f4304a88a69783ef87c50 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-07T22:41:00Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-c34eed7c9c8f4304a88a69783ef87c502024-02-23T15:08:42ZengMDPI AGBiomedicines2227-90592024-02-0112239410.3390/biomedicines12020394Addressing 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 MedicineAlexandra M. Stevens0Maci Terrell1Raushan Rashid2Kevin E. Fisher3Andrea N. Marcogliese4Amos Gaikwad5Pulivarthi Rao6Chelsea Vrana7Michael Krueger8Michael Loken9Andrew J. Menssen10Jacqueline A. Cook11Noah Keogh12Michelle Alozie13Hailey Oviedo14Alan K. Gonzalez15Tamilini Ilangovan16Julia Kim17Sohani Sandhu18Michele S. Redell19Section 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, USASection 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, USASection 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, USADepartment of Pathology & Immunology, Baylor College of Medicine, Genomic Medicine Division, Texas Children’s Hospital, Houston, TX 77030, USADepartment of Pathology & Immunology, Baylor College of Medicine, Laboratory Medicine Division, Texas Children’s Hospital, Houston, TX 77030, USASection 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, USASection 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, USASection 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, USASection 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, USAHematologics, Seattle, WA 98121, USAHematologics, Seattle, WA 98121, USAHematologics, Seattle, WA 98121, USASection 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, USASection 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, USASection 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, USASection 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, USASection 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, USASection 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, USASection 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, USASection 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, USAThe 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.https://www.mdpi.com/2227-9059/12/2/394PDX developmentChildren’s Oncology Group (COG)serial transplantingBCM PDX portalfuture developmentNSGS |
| spellingShingle | 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 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 Biomedicines PDX development Children’s Oncology Group (COG) serial transplanting BCM PDX portal future development NSGS |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | PDX development Children’s Oncology Group (COG) serial transplanting BCM PDX portal future development NSGS |
| url | https://www.mdpi.com/2227-9059/12/2/394 |
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