Contrasting effects of rh‐MIP‐1α and TGF‐β1on chronic myeloid leukemia progenitors in vitro

Autor: M. G. Freshney, D. J. Dunlop, Linda Richmond, E. Fitzsimons, Tessa L. Holyoake, A. M. Sproul, W. P. Steward, Ian M. Franklin, I. B. Pragnell, M.J. Alcorn
Rok vydání: 1993
Předmět:
Zdroj: Stem Cells. 11:122-128
ISSN: 1549-4918
1066-5099
Popis: In chronic myeloid leukemia (CML) an abnormality at the stem cell level results in unregulated expansion of myeloid progenitors. The mechanism underlying this uncontrolled proliferation remains unclear. An in vitro clonogenic assay which detects the human counterpart of the murine colony forming unit (CFU) CFU-A/CFU-S day 12 was described in a report of our recent findings. CML bone marrow samples were found to proliferate in the CFU-A assay, producing colonies morphologically indistinguishable from normal controls. The bcr/abl transcripts were sought in the RNA from individual colonies using the polymerase chain reaction (PCR). For the five CML samples tested to date, the majority of CFU-A colonies at diagnosis or in early chronic phase were found to be bcr/abl positive. For normal controls both macrophage inflammatory protein-1α (MIP-1α) and transforming growth factor-β1 (TGF-β1) inhibited the proliferation of CFU-A colonies when directly added to the assay. In contrast, CML progenitors responded normally to TGF-β1, but showed no response to MlP-1α. In suicide assays, for five normal bone marrow samples, CFU-A progenitors induced into S-phase returned to a quiescent state after treatment with MIP-1α. CML progenitors demonstrated inherently high cycle status which showed no definite response to MIP-1α. However, TGF-β1 resulted in quiescence of CML progenitor cycling. In conclusion, the primitive progenitors from CML samples were inhibited normally by TGF-β1 but showed no response to MIP-1α. Therefore, MIP-1α should have clinical potential as a protective agent during chemotherapy or for chemotherapeutic purging of CML bone marrow grafts in vitro, allowing selective killing of the malignant population.
Databáze: OpenAIRE
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