Spontaneous exodus of high numbers of normal early progenitor cells (Ph-negative LTC-IC) in the peripheral blood of patients with chronic myeloid leukaemia at the beginning of the disease.

Abstract

Elevated white blood cell counts are frequently found in patients with chronic myeloid leukaemia (CML). Although some studies have disclosed that bone marrow of CML patients may contain some normal Philadelphia-negative early progenitor cells, it has been assumed that the dramatic increase of white blood cells was entirely related to the leukaemic cell expansion. In this study we attempted to quantify the number of normal and leukaemic progenitor cells in the bone marrow and peripheral blood of newly diagnosed CML patients. Bone marrow and peripheral blood cells of eight newly diagnosed CML patients were analysed for clonogenic colony-forming cells (CFC) and very early progenitor cells, i.e. long-term culture initiating cells (LTC-IC). The leukaemic (Ph-positive) or normal (Ph-negative) origin of progenitor cells was revealed by cytogenetic analysis performed on single colonies arising from in-vitro assays. In 6/8 patients the marrow CFC frequency ranged from 400 to 9300/10(6) mononuclear cells (MNC), 0-50% being Philadelphia chromosome negative; the LTC-IC frequency ranged from 0 to 11/10(6) MNC, and were 80-100% Ph-negative. The corresponding absolute values into peripheral blood were: CFC = 1-35.5 x 10(3)/ml, 0-50% Ph-negative, and LTC-IC = 0-2.5 x 10(3)/ml, 0-100% Ph-negative. In one patient, no LTC-IC were detected in either the marrow or the peripheral blood. In conclusion, in the peripheral blood of some CML patients, the number of normal LTC-IC is more than 3 times the number of leukaemic progenitor cells, and is much higher (50 times) than the corresponding value found in normal subjects in steady state (2.5/ml v 124/ml). These data support the concept that leukaemic 'stem cells', with respect to normal ones, may be considerably fewer than previously thought. In addition it is shown that at the beginning of CML high numbers of normal LTC-IC are spontaneously mobilized into the blood. Finally, the presence of Ph-negative early progenitors into the blood may represent a potential source of normal stem cells available for autografting providing they can be separated from leukaemic cells.