Growth pattern and clinical correlation of subcutaneously inoculated human primary acute leukemias in severe combined immunodeficiency mice Journal Article
| Authors: | Yan, Y.; Salomon, O.; McGuirk, J.; Dennig, D.; Fernandez, J.; Jagiello, C.; Hai, N.; Collins, N.; Steinherz, P.; O'Reilly, R. J. |
| Article Title: | Growth pattern and clinical correlation of subcutaneously inoculated human primary acute leukemias in severe combined immunodeficiency mice |
| Abstract: | We examined the ability of patient-derived human leukemic blasts to generate leukemic growth and dissemination in severe combined immunodeficiency (SCID) mice by subcutaneous inoculation without conditioning treatment or administration of growth-promoting cytokines. Additionally, we correlated the growth pattern with the clinical outcome of patients from whom the leukemic cells were derived. The leukemias displayed three distinct growth patterns, ie, either aggressive, indolent, or no tumor growth. Leukemic cells from 6 of 13 patients with acute myeloid leukemia (AML), 4 of 7 T-cell acute lymphoblastic leukemia (T-ALL), and 11 of 16 patients with B- lineage ALL grew as subcutaneous tumors, with a significant number subsequently disseminating into distant organs in SCID mice. Patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SCID mice had a relatively poor clinical outcome, whereas patients with AML and T- or B-lineage ALL whose leukemic blasts grew indolently or whose cells failed to induce growth had a more favorable clinical course. Our study has shown that the subcutaneous inoculation of patient-derived human leukemic cells in SCID mice can engraft and grow as subcutaneous tumors with subsequent dissemination to distant organs in a manner analogous to their pattern of growth in humans. Additionally, these data suggest a clinical correlation to the growth and dissemination of some leukemic subtypes that may represent not only an additional prognosticator for patient outcome, but also a vehicle for the study of the biologic behavior of human leukemias and the development of novel therapeutic strategies. |
| Keywords: | disease-free survival; promoter region; nonhuman; mouse; animals; mice; animal tissue; disease association; gene expression; cell growth; animal experiment; animal model; mice, scid; acute lymphoblastic leukemia; acute leukemia; disease progression; leukemia, myeloid; neoplasm metastasis; transplantation, heterologous; neoplasm invasiveness; graft survival; neoplasm transplantation; tumor growth; injections, subcutaneous; combined immunodeficiency; acute disease; tumor stem cells; leukemia, t-cell, acute; humans; prognosis; priority journal; article; leukemia, b-cell, acute |
| Journal Title: | Blood |
| Volume: | 88 |
| Issue: | 8 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 1996-10-01 |
| Start Page: | 3137 |
| End Page: | 3146 |
| Language: | English |
| PUBMED: | 8874214 |
| PROVIDER: | scopus |
| DOI: | 10.1182/blood.V88.8.3137.bloodjournal8883137 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
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