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

Authors

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

Language

English

Publication Date

2-8-2024

Journal

Biomedicines

DOI

10.3390/biomedicines12020394

PMID

38397996

PMCID

PMC10886789

PubMedCentral® Posted Date

2-8-2024

PubMedCentral® Full Text Version

Post-print

Abstract

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.

Keywords

PDX development, Children’s Oncology Group (COG), serial transplanting, BCM PDX portal, future development, NSGS, MISTRG, MISTRG6, novel therapeutics

Published Open-Access

yes

Recommended Citation

Stevens, Alexandra M; Terrell, Maci; Rashid, Raushan; et al., "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" (2024). Faculty and Staff Publications. 5625.
https://digitalcommons.library.tmc.edu/baylor_docs/5625