title: Circulating thrombopoietin as an in vivo growth factor for blast cells in acute myeloid leukemia.
abstract: Thrombopoietin (TPO), the major growth factor for cells of the megakaryocytic lineage, is removed from circulation by binding to c-mpl receptors present on platelets and megakaryocytes. We studied patients with acute lymphoblastic leukemia (ALL) or acute myeloblastic leukemia (AML) and used TPO-induced c-fos protein up-regulation as a marker of c-mpl functionality and observed that c-mpl-presenting blast cells were present in 62% (37 of 60) of patients with ALL but that c-mpl was nonfunctional in 0 of 28 patients and that they were present in 56% (22 of 39) of patients with AML and were functional in 43% (12 of 28). Adequate increases in serum TPO level in response to thrombocytopenia were seen in patients with ALL and with c-mpl-deficient (c-mpl-) AML. In contrast, in patients with c-mpl-proficient (c-mpl+) AML, TPO levels were found to be inappropriately low but increased to expected values during induction chemotherapy as blasts disappeared. In vitro significant TPO-associated blast cell proliferation or decreased apoptosis was observed only in patients with c-mpl+ AML compared with ALL or c-mpl- AML and was highly correlated with low in vivo TPO levels (P < .001). These data suggest that, in patients with AML, inadequate TPO levels are secondary to TPO clearing by functional c-mpl receptor myeloid blast cells and that TPO may serve as an in vivo myeloid leukemic growth factor in a significant number of patients.
authors.affiliation: Laboratory of Hematology, CHU-Brugmann, 4 Place Van Gehuchten, B-1020 Brussels, Belgium. francis.corazza@ulb.ac.be
authors.forename: Francis
authors.initials: F
authors.lastname: Corazza
authors.forename: Christophe
authors.initials: C
authors.lastname: Hermans
authors.forename: Stéphanie
authors.initials: S
authors.lastname: D'Hondt
authors.forename: Alina
authors.initials: A
authors.lastname: Ferster
authors.forename: Alain
authors.initials: A
authors.lastname: Kentos
authors.forename: Yves
authors.initials: Y
authors.lastname: Benoît
authors.forename: Eric
authors.initials: E
authors.lastname: Sariban
mesh_terms: D000208:Acute Disease; D017209:Apoptosis; D001752:Blast Crisis / Q000097:blood / Q000473:pathology*; D049109:Cell Proliferation; D006133:Growth Substances / Q000097:blood; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000209:etiology / Q000473:pathology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000209:etiology / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000502:physiology; D018121:Receptors, Cytokine / Q000032:analysis / Q000502:physiology; D053628:Receptors, Thrombopoietin; D013921:Thrombocytopenia / Q000097:blood; D013926:Thrombopoietin / Q000097:blood*
chemical_list: D006133:Growth Substances; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D013926:Thrombopoietin