Blood Journal
Leading the way in experimental and clinical research in hematology

Circulating thrombopoietin as an in vivo growth factor for blast cells in acute myeloid leukemia

  1. Francis Corazza,
  2. Christophe Hermans,
  3. Stéphanie D'Hondt,
  4. Alina Ferster,
  5. Alain Kentos,
  6. Yves Benoît, and
  7. Eric Sariban
  1. From the Laboratory of Hematology, Brugmann University Hospital, Brussels; the Laboratory of Pediatric Oncology and Hematology-Oncology Unit, Hôpital Universitaire des Enfants, Brussels; the Hematology Department, Erasme University Hospital, Brussels; and the Pediatric Oncology Department UZ-Ghent, Belgium.

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. (Blood. 2006; 107:2525-2530)

  • Submitted June 28, 2005.
  • Accepted November 7, 2005.
View Full Text