Leptin in human acute myelogenous leukemia: studies of in vivo levels and in vitro effects on native functional leukemia blasts.
OBJECTIVE
Leptin receptors can be expressed by acute myelogenous leukemia (AML) cells, but the functional effects of leptin on native AML blasts have not been characterized in detail. We investigated systemic leptin levels in AML patients and in vitro effects of leptin on cultured AML blasts.


METHODS
Serum leptin levels were compared for patients with untreated AML and healthy controls. Native AML blasts were derived from a large group of consecutive patients, and effects of leptin on proliferation (suspension cultures and colony formation), constitutive cytokine secretion, differentiation and apoptosis regulation were assayed in vitro.


RESULTS
Systemic leptin levels were decreased in patients with untreated AML, and leptin levels in acute leukemia patients were not altered during severe chemotherapy-induced cytopenia and complicating febrile neutropenia. In vitro studies demonstrated that leptin increased AML blast release of interleukin (IL) 1beta, IL6, tumor necrosis factor (TNF) alpha and granulocyte-macrophage colony-stimulating factor (GM-CSF). This enhancing effect showed no correlation with CD34 expression and was not dependent on the presence of serum, induction of differentiation or alteration of caspase 3 activity with decreased in vitro apoptosis. Leptin also increased spontaneous AML blast proliferation, whereas divergent effects on blast proliferation were observed in the presence of exogenous cytokines. The in vitro effects were usually observed at concentrations exceeding the systemic levels.


CONCLUSIONS
Our results suggest that systemic leptin levels alone do not have a major influence on native AML blasts, but the systemic levels in combination with local leptin release in the bone marrow may affect the functional characteristics of these cells.
Bruserud
Øystein
Ø
Medical Department, Haukeland University Hospital, N-5021 Bergen, Norway. oystein.bruserud@haukeland.no
Huang
Tien-sheng
TS
Glenjen
Nils
N
Gjertsen
Bjørn Tore
BT
Foss
Brynjar
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000473:pathology; D008297:Male; D008875:Middle Aged
D016207:Cytokines; D020738:Leptin