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Selective Expansion of Primitive Normal Hematopoietic Cells in Cytokine-Supplemented Cultures of Purified Cells From Patients With Chronic Myeloid Leukemia
| Content Provider | Scilit |
|---|---|
| Author | Petzer, A. L. Eaves, C. J. Barnett, M. J. Eaves, A. C. |
| Copyright Year | 1997 |
| Description | We have previously reported that primitive normal hematopoietic cells detectable as long-term culture-initiating cells (Ph-LTC-IC) are present at high levels in the blood of some patients with chronic myeloid leukemia (CML). We now show that this population can be expanded several-fold when highly purified CD34+CD38− cells isolated from the blood of such patients are cultured for 10 days in a serum-free medium containing 100 ng/mL of Flt3-ligand and Steel factor and 20 ng/mL of interleukin-3 (IL-3) and IL-6, and granulocyte colony-stimulating factor. In similar cultures initiated with CD34+CD38− cells from CML blood samples in which all of the LTC-IC were leukemic (Ph+), Ph+ LTC-IC activity was rapidly lost both in the presence and absence of admixed CD34+CD38− cells isolated from normal marrow. Conversely, the ability of normal LTC-IC to expand their numbers was shown to be independent of the presence of Ph+LTC-IC and later types of Ph+colony-forming cell (CFC) progenitors. In contrast to the LTC-IC, CFC were consistently -a m p l i f i e d i n c u l t u r e s i n i t i a t e d w i t h C M L - d e r i v e d -CD34+CD38− cells and the additional CFC present after 10 days were, like the starting population of CFC, almost exclusively Ph+ regardless of the genotype(s) of the LTC-IC in the original CML samples. Amplification of the Ph+CFC population in these cultures showed the same factor dependence as previously demonstrated for the in vitro expansion of CFC from normal marrow CD34+CD38− cells. Ph+LTC-IC disappeared regardless of the cytokines present. Taken together these findings support a model of CML in which the leukemic stem cells are characterized by a decreased probability of self-renewal and an increased probability of differentiation. In addition, they suggest new opportunities for improving the treatment of CML using strategies that require autologous stem cell rescue. |
| Related Links | https://ashpublications.org/blood/article-pdf/90/1/64/1038834/64.pdf |
| Ending Page | 69 |
| Page Count | 6 |
| Starting Page | 64 |
| DOI | 10.1182/blood.v90.1.64 |
| Journal | Blood |
| Issue Number | 1 |
| Volume Number | 90 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 1997-07-01 |
| Access Restriction | Open |
| Subject Keyword | Immunology Hematopoietic Cd34 Cultures Cd38 Leukemic Ltc Ic Previously Normal Marrow Journal: Blood (Vol- 11, Issue- 1) |
| Content Type | Text |
| Resource Type | Article |
