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A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Kuehnle, Ingrid Weidner, Douglas Andreeff, Michael |
| Copyright 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) |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.bloodjournal.org/content/bloodjournal/98/4/1166.full.pdf?sso-checked=true |
| PubMed reference number | 11493466v1 |
| Volume Number | 98 |
| Issue Number | 4 |
| Journal | Blood |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Bone Marrow Cytostatic Agents Daunorubicin Diabetic Neuropathies Drug Efflux Dyes Eighty Hematopoietic stem cells Immunologic Deficiency Syndromes Immunophenotyping Leukemia, Myelocytic, Acute Leukemic Hematopoietic Stem Cell Leukemic Infiltration Mitoxantrone Myeloid Leukemia Patients SCID Mice Subgroup Transplanted tissue |
| Content Type | Text |
| Resource Type | Article |
