Proliferating status of peripheral blood progenitor cells from patients with BCR/ABL-positive chronic myelogenous leukemia

To investigate the mechanisms behind the leukemic expansion of BCR/ABL-posi tive chronic myelogenous leukemia (CML), we examined the cell cycle status of hematopoietic progenitor cells from peripheral blood (PB) and bone marro w (BM) of 37 patients with newly diagnosed BCR/ABL-positive CML, We found a high proportion of 12.51 +/- 1.19% of CD34(+) peripheral blood progenitor cells (PBPC) in S/G(2)M phase. Comparison of PB and BM from 19 cases reveal ed similar proliferation rates (10.74 +/- 1.41% vs 15.97 +/- 1.95%), Furthe rmore, even primitive CD34(+)/CD38(-) PBPC displayed high proliferation rat es (17.45 +/- 2.98%) in 10 cases examined. In contrast, PBPC from 11 patien ts with BCR/ABL-negative myeloproliferative disorders were almost noncyclin g (S/G(2)M 1.46 +/- 0.47%), When matched pairs of PB and BM from six patien ts with BCR/ABL-negative myeloproliferative disorders were examined, only 0 .89 +/- 0.41% of the CD34(+) PBPC, but 8.29 +/- 3.13% CD34(+) cells from BM were in S/G(2)M phase. Consistently, as compared to 19 patients with newly diagnosed BCR/ABL-positive CML, a significantly lower PBIBM ratio of CD34( +) cells in S/G(2)M phase was found in these six patients with BCR/ABL-nega tive myeloprolifrative disorders. Administration of the tyrosine kinase inh ibitor STI571 to 13 patients with CML in chronic phase, accelerated phase, or blast crisis lead to an inhibition of PBPC proliferation within a few da ys. Interestingly, CD34(+) hematopoietic progenitor cells from BM remained proliferating in five cases examined, indicating that CML PBPC are more eas ily inhibited by STI571 as compared to CD34(+) CML hematopoietic progenitor cells from BM, These data suggest that BCR/ABL leads to an enhanced cell c ycle activation of CD34(+) cells, which seems to be, at least in part, inde pendent of additional factors provided by the bone marrow microenvironnent.