Circulating levels of thrombopoietic and inflammatory cytokines in patients with acute myeloblastic leukemia and myelodysplastic syndrome.
BACKGROUND
The regulation of megakaryocytopoiesis and thrombopoiesis appears to be under the control of an array of hematopoietic growth factors. The regulatory mechanism of endogenous cytokines in circulating platelet counts of thrombocytopenic patients with acute myeloblastic leukemia (AML) and myelodysplastic syndrome (MDS) is still not clear.


METHODS
We measured the serum levels of both thrombopoietic and inflammatory cytokines in peripheral blood and bone marrow samples collected from 52 patients with either AML or MDS along with 35 normal control samples. The levels of thrombopoietin (TPO), interleukin (IL)-11, IL-6, IL-8 and stem cell factor (SCF) were determined by ELISA.


RESULTS
Platelet counts in the AML/MDS patients during initial diagnosis, chemotherapy and complete remission were 71.2 +/- 11.6, 47.2 +/- 6.1 and 181.4 +/- 26.3 x10(9)/l, respectively. The median value of TPO in AML/MDS patients during diagnosis was 150.6 pg/ml and increased significantly during chemotherapy (median: 828 pg/ml; p < 0.05) but then decreased following complete remission (median: 221.4 pg/ml). However, these levels were all significantly higher in patients than in normal subjects (p < 0.05, p < 0.05 and p < 0.05; respectively), and no significant change was noted in the levels of IL-11 and SCF during treatment of patients or in normal controls. The level of IL-6 was not detectable in normal serum samples but was markedly increased in the AML/MDS patients (median level during diagnosis: 6.7 pg/ml; chemotherapy: 25 pg/ml; complete remission: 7 pg/ml). The level of IL-8 in patients with AML and MDS was markedly elevated during diagnosis (median: 27.5 pg/ml; range: 0-1,587 pg/ml), but decreased to the level of the normal controls when patients were under chemotherapy or in complete remission.


CONCLUSIONS
The endogenous levels of TPO, IL-6 and IL-8 are elevated in the thrombocytopenic patients with AML and MDS. Our results are consistent with previous mechanistic studies and suggest that TPO and IL-6 may be active mediators of platelet production.
Division of Hematology, Department of Medicine, Veterans General Hospital-Taipei and National Yang-Ming University, Taipei, Taiwan, ROC.
Hui-Chi
HC
Hsu
Yuan-Ming
YM
Lee
Wen-Hui
WH
Tsai
Mei-Lan
ML
Jiang
Chau-Hung
CH
Ho
Chi-Kuan
CK
Ho
Sheng-Yuan
SY
Wang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood*; D004358:Drug Therapy; D006801:Humans; D017370:Interleukin-11 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000188:drug therapy; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood* / Q000188:drug therapy; D010976:Platelet Count; D019089:Stem Cell Factor / Q000097:blood; D013926:Thrombopoietin / Q000097:blood
D000970:Antineoplastic Agents; D016207:Cytokines; D017370:Interleukin-11; D015850:Interleukin-6; D016209:Interleukin-8; D019089:Stem Cell Factor; D013926:Thrombopoietin