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A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia.
- Source :
-
Blood [Blood] 2001 Aug 15; Vol. 98 (4), pp. 1166-73. - Publication Year :
- 2001
-
Abstract
- The hematopoietic stem cell underlying acute myeloid leukemia (AML) is controversial. Flow cytometry and the DNA-binding dye Hoechst 33342 were previously used to identify a distinct subset of murine hematopoietic stem cells, termed the side population (SP), which rapidly expels Hoechst dye and can reconstitute the bone marrow of lethally irradiated mice. Here, the prevalence and pathogenic role of SP cells in human AML were investigated. Such cells were found in the bone marrow of more than 80% of 61 patients and had a predominant CD34(low/-) immunophenotype. Importantly, they carried cytogenetic markers of AML in all 11 cases of active disease examined and in 2 out of 5 cases in complete hematological remission. Comparison of daunorubicin and mitoxantrone fluorescence emission profiles revealed significantly higher drug efflux from leukemic SP cells than from non-SP cells. Three of 28 SP cell transplants generated overt AML-like disease in nonobese diabetic--severe combined immunodeficient mice. Low but persistent numbers of leukemic SP cells were detected by molecular and immunological assays in half of the remaining mice. Taken together, these findings indicate that SP cells are frequently involved in human AML and may be a target for leukemic transformation. They also suggest a mechanism by which SP cells could escape the effects of cytostatic drugs and might eventually contribute to leukemia relapse. (Blood. 2001;98:1166-1173)
- Subjects :
- Acute Disease
Adolescent
Adult
Aged
Aged, 80 and over
Animals
Antibiotics, Antineoplastic pharmacokinetics
Antineoplastic Agents pharmacokinetics
Benzimidazoles pharmacokinetics
Cell Separation
Child
Child, Preschool
Daunorubicin pharmacokinetics
Drug Resistance
Female
Humans
Immunophenotyping
Infant
Leukemia, Myeloid drug therapy
Leukocytes, Mononuclear
Male
Mice
Mice, Inbred NOD
Middle Aged
Mitoxantrone pharmacokinetics
Myelodysplastic Syndromes drug therapy
Myelodysplastic Syndromes pathology
Neoplasm Transplantation
Neoplasms, Second Primary
Stem Cell Transplantation
Stem Cells drug effects
Tumor Cells, Cultured drug effects
Tumor Cells, Cultured transplantation
Leukemia, Myeloid pathology
Stem Cells pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 98
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 11493466
- Full Text :
- https://doi.org/10.1182/blood.v98.4.1166