Proliferative effects of several hematopoietic growth factors on acute myelogenous leukemia cells and correlation with treatment outcome

Abstract

The response of human acute myelogenous leukemia (AML) cells to four different hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 ␤ (IL-1␤), interleukin-3 (IL-3), and stem cell factor (SCF)) and the relationship of the proliferative response of the AML cells to treatment outcome were studied. Proliferative responses were analyzed in 79 patients with de novo AML and 19 patients with AML arising from myelodysplastic syndrome (MDS). In de novo AML, a positive proliferative response (stimulation index Ͼ2) was seen in 65 to 75% of cases. AML cells arising from MDS had a much higher incidence of proliferative response to each growth factor (79 to 90%) and a much higher level of 3 H-TdR incorporation. The relationship to treatment outcome was evaluated in 79 patients with de novo AML. The patients whose leukemic cells had a positive proliferative response to any growth factor, especially IL-3 and SCF, had a poorer outcome, ie a lower complete remission (CR) rate, shorter CR duration, and shorter survival. The outcome was particularly poor in patients whose leukemic cells had proliferative responses to all four or any of the growth factors, compared to patients whose leukemic cells had no response. This increased response may be a marker of poor prognosis in patients with AML.

Cytogenetic subgroups in acute myeloid leukemia differ in proliferative activity and response to GM-CSF

“…43 Sensitivity of blast cells to GM-CSF in vitro appeared to be inversely related with early treatment response which may be explained by the autocrine production of hematopoietic growth factors in AML blasts. [44][45][46][47] These results were confirmed by Tsuzuki and coworkers, 48 showing that patients whose leukemic cells had a positive proliferative response to growth factors had a poorer outcome.…”

Biological characteristics and prognosis of adult acute myeloid leukemia with internal tandem duplications in the Flt3 gene

“…A similar, though less significant, correlation was also observed in cytokine-stimulated cultures. 44 It therefore seems opportune to re-evaluate a large group of AML samples, that exclude patients carrying a Flt3/ITD mutation, with respect to growth factor response and patient prognosis.…”

Improved prognostic significance of cytokine-induced proliferation in vitro in patients with de novo acute myeloid leukemia of intermediate risk: impact of internal tandem duplications in the Flt3 gene

“…26,27 Correlations between the in vitro cytokine responsiveness and patient prognosis have been previously been reported. [28][29][30] Our observation that patients with a Flt3/ITD comprise a 'low' cytokine responder population coupled to a poor prognosis, combined with the poor prognosis of patients with an age over 60 years, led us to define our intermediate risk population as that population of primary AML patients with an age below 60 years not having a tandem duplication in the Flt3 gene and with intermediate risk cytogenetics. Here, we show that among this intermediate risk population, poor and good risk patient prognosis can be further stratified based on the short-term (7-day) in vitro response to either G-CSF or IL-1␣.…”