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.

journal_name

Blood

journal_title

Blood

authors

Corazza F,Hermans C,D'Hondt S,Ferster A,Kentos A,Benoît Y,Sariban E

doi

10.1182/blood-2005-06-2552

subject

Has Abstract

pub_date

2006-03-15 00:00:00

pages

2525-30

issue

6

eissn

0006-4971

issn

1528-0020

pii

2005-06-2552

journal_volume

107

pub_type

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