BCR-ABL expression in different subpopulations of functionally characterized Ph+ CD34+ cells from patients with chronic myeloid leukemia
| Autor: | V, Maguer-Satta, A L, Petzer, A C, Eaves, C J, Eaves |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Adult
Male Molecular Sequence Data Immunology Fusion Proteins bcr-abl Antigens CD34 Cell Separation Polymerase Chain Reaction Biochemistry Immunophenotyping Antigens CD Leukemia Myelogenous Chronic BCR-ABL Positive hemic and lymphatic diseases Receptors Transferrin Humans RNA Messenger ADP-ribosyl Cyclase N-Glycosyl Hydrolases Membrane Glycoproteins Base Sequence Gene Expression Regulation Leukemic HLA-DR Antigens Cell Biology Hematology Middle Aged Hematopoietic Stem Cells ADP-ribosyl Cyclase 1 Antigens Differentiation Antigens Differentiation B-Lymphocyte Neoplastic Stem Cells Thy-1 Antigens Female |
| Zdroj: | Blood. 88:1796-1804 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v88.5.1796.bloodjournal8851796 |
| Popis: | In patients with chronic myeloid leukemia (CML), the leukemic (BCR- ABL+/Ph+) clone typically includes cells belonging to all of the myeloid lineages and frequently some B cells. From such observations it has been inferred that the initial BCR-ABL gene rearrangement event occurs in a pluripotent hematopoietic stem cell and that the clone subsequently generated is maintained by a subpopulation of neoplastic, BCR-ABL-expressing cells that retain at least some of the defining properties of normal hematopoietic stem cells. To test this hypothesis directly, we isolated various subpopulations of CD34+ cells from fresh or cryopreserved samples of peripheral blood from 5 CML patients with high white blood cell counts, 4 of which were selected because of their exclusive content of Ph+ progenitors (both colony-forming cells and long-term culture-initiating cells [LTC-IC]). Cells in each of the CD34+ subpopulations isolated were examined for the presence of BCR-ABL mRNA using a reverse transcriptase-polymerase chain reaction technique that reproducibly gave a positive signal from single K562 cells. BCR- ABL mRNA was detected in 117 of 147 samples (80%) in which actin mRNA was demonstrable. This included 60% to 90% of a large number of individually analyzed CD34+ cells including 46 single CD34+CD71-CD38- cells and 27 single CD34+CD71+CD38+ cells from 3 patients. In 2 of these cases, the same populations also contained a very high frequency of Ph+ LTC-IC. Our findings demonstrate BCR-ABL gene expression in neoplastic cells with functional as well as surface marker characteristics of very primitive normal hematopoietic cells. This implicates the BCR-ABL gene product directly in the acquisition by these cells of properties that alter their interactions with the microenvironment and deregulate their proliferation control. |
| Databáze: | OpenAIRE |
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