The Expression Of Granulocyte Colony-Stimulating Factor Receptor Isoform â…  In Myeloid Leukemia Cells And Its Clinical Significance

Objective：To investigate the expression of G-CSFR isoform Ⅰ in myeloid leukemiacells and its clinical significance.Methods：1. Bone marrow were obtained from110AML(non-APL) patients,including89initial treatment cases and21remission cases. Bone marrow from9cases haematologically normal individuals were collected as normal control. Bonemarrow mononuclear cells were isolateded by Ficoll-Hypaque centrifugation.2.Mononuclear cells from peripheral blood of13cases AML(non-APL) patients werecollected. Mononuclear cells from bone marrow of10cases haematologically normalindividuals were collected as normal control. And CD34+cells were sorted using flowcytometery.3. The mRNA expression of G-CSFR isoform Ⅰ on these cells wasmeasureed by QRT-PCR.4. The mRNA expression changes of G-CSFR isoform ⅠmRNA on HL-60and U937cells induced by ATRA was measured by QRT-PCR.5.MTT and flow cytometry were used to detect the proliferation and differentiationeffect of G-CSF on HL-60and U937cells with up-regulation of G-CSFR isoform Ⅰinduced by ATRA.Results:1. The expression of G-CSFR isoform Ⅰ in initial treatment subgroup waslower than remission subgroup and control group(P＜0.05). Besides,11out of12AML patients expressed lower G-CSFR isoform Ⅰ mRNA during the initial treatmentperiod than remission period (P＜0.05). The expression of G-CSFR isoform Ⅰ onAML CD34+cells was also lower than normal control CD34+cells and AML cellswithout sorting(P＜0.05).2. The expression of G-CSFR isoform Ⅰ in AML patientswere negatively related to the count of peripheral white blood cell(r=-0.290, p <0.01)and the proportion of immature blood cells (r=-0.362, p <0.01). Ⅰn other word, lowerexpression of G-CSFR isoform Ⅰ in AML patients couples with higher WBC countand proportion of immature cells. Besides, there was no significant differencebetween different FAB subtype of AML patients.3.ATRA treatment can promote the mRNA expression of G-CSFR isoform Ⅰ on HL-60and U937cells markedly,followed by growth inhibition and differentiation induction(P＜0.01).4.G-CSFtreatment can promote the growth of HL-60and U937cells（P＜0.05） withoutdifferentiation induction effect. ATRA can inhibit the growth promotion effect ofG-CSF（P＜0.01）. G-CSF combined with ATRA can potentiate the differentiationeffect on HL-60and U937cells（P＜0.05）. The differentiation inbition effect ofG-CSF after24hours ATRA treatment on HL-60and U937cells was moreapparently than using G-CSF and ATRA at the same time，although the difference hasno statistically significant.Conclusion：1. The expression of G-CSFR isoform Ⅰ in AML initial treatmentsubgroup was lower than remission subgroup and healthy control group. Lowerexpression of G-CSFR isoform Ⅰ in AML patients couples with higher WBC countand proportion of immature cells.2. G-CSF can potentiate the differentiation effect onHL-60and U937cells with up-regulation of G-CSFR isoform Ⅰ induced by ATRA.