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Impaired megakaryopoiesis in patients with chronic idiopathic neutropenia is associated with increased transforming growth factor β 1 production in the bone marrow
Author(s) -
Psyllaki Maria,
Damianaki Athina,
Gemetzi Claudia,
Pyrovolaki Katerina,
Eliopoulos George D.,
Papadaki Helen A.
Publication year - 2006
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2006.06242.x
Subject(s) - megakaryocyte , thrombopoietin , progenitor cell , bone marrow , cd34 , clonogenic assay , peripheral blood mononuclear cell , granulocyte colony stimulating factor , megakaryocytopoiesis , medicine , endocrinology , growth factor , immunology , stem cell factor , andrology , haematopoiesis , biology , stem cell , cell , receptor , in vitro , chemotherapy , biochemistry , genetics
Summary Patients with chronic idiopathic neutropenia (CIN) display relatively low peripheral blood platelet counts and hypo‐lobulated megakaryocytes in the bone marrow (BM). The underlying pathogenetic mechanismswere probed by studying the reserves and clonogenic potential of BM megakaryocytic progenitor cells using flow‐cytometry and a collagen‐based clonogenic assay for the identification of megakaryocyte colony‐forming units (CFU‐Meg). Thrombopoietin (TPO) and transforming growth factor‐ β 1 (TGF β 1) levels were also evaluated in long‐term BM culture supernatants using an enzyme‐linked immunosorbent assay. CIN patients ( n = 39) showed a low proportion of BM CD34 + /CD61 + megakaryocytic progenitor cells and low frequency of early and mixed CFU‐Meg in the BM mononuclear, but not CD34 + , cell fraction, compared with healthy controls ( n = 20). TPO and TGF β 1 levels were significantly higher in patients compared with controls. TPO levels inversely correlated with platelet counts whereas TGF β 1 values correlated inversely with CD34 + /CD61 + and CFU‐Meg megakaryocytic progenitor cell numbers and positively with TPO levels. The addition of an anti‐TGF β 1 neutralising antibody significantly increased the numbers of CFU‐Meg in CIN patients but not in controls, compared with baseline. These data suggest that increased local production of TGF β 1 probably affects the BM megakaryocytic progenitor cell growth in CIN whereas the compensatory production of TPO finally balances the TGF β 1‐induced inhibitory effect.