CD34+ stem cells in chronic myeloproliferative disorders

Abstract

Contrasting the wealth of information that is available about various biological and therapeutic aspects of human CD34+ stem cells, little data ex i s t concerning their quantity and dynamics as well as their mutual relationships with other hematopoietic constituents in the bone marrow of patients with chronic m y e l o p r o l i f e r a t ive disorders. In comparison with a control group frequency of progenitors is signifi c a n t l y increased in chronic myeloid leukemia (CML). Following different therapeutic modalities their quantity reflects therapeutic eff i c a cy (responder and nonresponder patients) and therefore exerts a predictive value regarding acceleration and blastic crisis. The s i g n i ficant correlations between fiber content and number of these precursors elucidates the complex interactions between stroma and progenitor cell d i fferentiation and maturation. Fo l l owing allogeneic bone marrow transplantation there is a rapid recovery of the CD34+ stem cell population in the first month. A higher number of these cells is related with graft size, an earlier independence for platelet transfusion and a more extended regeneration of erythro- and megakaryopoiesis. The slight increase in reticulin fibers in these patients may be associated with the complex and so far illd e fined pathomechanism of homing (adherence to the fibrous matrix). In idiopathic myelofibrosis (IMF) an increased number of CD34 + stem cells is found predominantly in the early (prefibrotic or mild fibrotic) hypercellular stages and probably indicates a higher p r o l i f e r a t ive activity of the precursor cell pool. According to sequential biopsies most patients with early IMF that later evolved into an overt fibrosclerotic stage usually display a reduction of progenitor cells during the development of myelofibrosis. The unequal d i s t r i bution of CD34+ stem cells in the bone marrow versus spleen in IMF (advanced fibrosclerotic stage) is in support of the currently discussed hypothesis of splenic filtration and concentration of precursor cells as an essential feature of myeloid metaplasia. Rega r d i n g prognosis in CML a higher amount of CD34+ stem cells is significantly associated with an unfavorable survival and thus confirms the assumed implication of an accelerated phase of disease at onset. On the other hand, in polycythemia vera (PV) and IMF a low number of progenitors is probably due to a decreased proliferation rate (reduced hematopoietic turnover index) and therefore reflects a reduction in the regenerative capacity of hematopoiesis. For this reason, a presumptive defect in the recovery of normal and clonally transformed stem cells is speculated to add to the worsening of prognosis by causing the well-known bone marrow insufficiency in terminal stage PV and IMF.