Reduction of clonal genetically unstable cells is the main therapeutic goal in chronic myeloid leukemia (CML) as it is thought to bt necessary for reducing the rate of secondary genetic changes and, thereby, for postponing blast crisis. We have shown that Ph-negative blood progenitor cells (BPC) can be collected by leukapheresis during early recovery after chemoterapy-induced marrow aplasia and that these cells are able to restore normal polyclonal hemopoiesis after autografting. As we have also shown that the best clinical results are achieved in patients autografted with Ph-negative BPC, the degree of the tumor burden in BPC could correlate with a prolongation in survival. In order to estimate the level of contamination with residual BCR-ABL positive cells, leukapheresis-collected peripheral blood mononuclear cells (PBMC) have been monitored by competitive reverse transcriptase-polymerase chain reaction (RT-PCR) for Phchromosome originated BCR-ABL transcripts. The tested leukapheresis-collected PBMC were from four patients; 100% cytogenetically Ph-negative PBMC were recovered from three of them, while PBMC from the fourth patient showed to have degrees of cytogenetically detectable Ph-positive cells. In the three patients with Ph-negative PBMC, competitive RT-PCR showed that, in cells from the first leukapheresis, BCR-ABL transcripts were under the threshold of 104/jig RNA, while the number of BCR-ABL transcripts increased in successive leukaphereses from two patients and remained under the threshold in the third one. PBMC from the partially Ph-positive patient showed little variation in level of BCR-ABL transcripts as in all leukaphereses at least 3 × 104 transcripts/ng RNA were found. According to other previous observations, also these preliminary data seem to suggest that normal Ph-negative progenitor cells increase in peripheral blood earlier than leukemic Ph-positive ones and that the combination of cytogenetics and molecular methods may significantly improve the ability to monitor the tumor burden in leukapheresiscollected PBMC.
|Number of pages||1|
|Publication status||Published - 1997|
ASJC Scopus subject areas
- Cancer Research
- Cell Biology