Patient-derived intrafemoral orthotopic xenografts of peripheral blood or bone marrow from acute myeloid and acute lymphoblastic leukemia patients: clinical characterization, methodology, and validation

Abstract

Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are malignant clonal diseases of the hematopoietic system with an unsatisfactory overall prognosis. The main obstacle is the increased resistance of AML and ALL cells to chemotherapy. The development and validation of new therapeutic strategies for acute leukemia require preclinical models that accurately recapitulate the genetic, pathological, and clinical features of acute leukemia. A patient-derived orthotopic xenograft (PDOX) model is established using surgical orthotopic implantation. They closely resemble human tumor progression and microenvironment and are more reliable translational research tools than subcutaneous-transplant models. In this study, we established PDOX models by direct intrafemoral injection of bone marrow and peripheral blood cells from AML and ALL patients, characterized their pathology, cytology, and genetics, and compared the model's characteristics and drug responsiveness with those of the corresponding patients.

Intrafemoral Injection of Human Hematopoietic Stem and Progenitor Cells into Immunocompromised Mice

“…For example, Medyouf and colleagues found that the addition of patient-derived mesenchymal stromal cells improved engraftment of CD34 + cells from patients with Myelodysplastic syndromes after intrafemoral injection 16 . Intrafemoral injections are also commonly employed to test leukemic engraftment of Acute Myeloid Leukemia 17 , 18 and Acute Lymphoblastic Leukemia samples 19 , 20 . Finally, intrafemoral injections have been used in a recent clinical trial of hematopoietic stem cell gene therapy of adult and pediatric patients affected by transfusion-dependent ß-thalassemia 21 , demonstrating their clinical relevance.…”