Cytokine expression in adherent layers from patients with myelodysplastic syndrome and acute myelogenous leukemia.
We have previously shown that long-term cultures of adherent layers derived from patients with chronic myelogenous leukemia in blast crisis express high levels of interleukin (IL)-1 beta and that this cytokine may participate in disease progression. In this study, we analyzed cytokine expression in bone marrow adherent layers derived from patients with myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). IL-6 messenger RNA (mRNA) was expressed in adherent layers established from four of nine MDS patients, and from 10 of 17 AML patients (including all four individuals in whom AML had evolved from an antecedent MDS state). Similarly, IL-1 beta mRNA was expressed in adherent layers derived from two of nine MDS patients and from three of 17 AML patients. Cultures from two of 10 AML patients who expressed IL-6 also expressed granulocyte (G) colony-stimulating factor (CSF) mRNA. In contrast, IL-1 beta, IL-6, and G-CSF mRNA were not discernible in adherent layers from any of 14 normal volunteers. Transforming growth factor-beta 1, macrophage (M) CSF, IL-7, and leukemia inhibitory factor mRNA as well as IL-6 protein were constitutively expressed in adherent layers derived from both MDS patients, AML patients, and normal bone marrows, whereas IL-1 alpha, tumor necrosis factor-alpha, and GM-CSF were not expressed in either the normal-, MDS- or AML-derived adherent layers. These results indicate that cultured stroma from a subset of MDS and AML patients produce IL-1 beta and/or IL-6. Although, exposure of adherent layers to exogenous IL-1 beta was able to induce IL-6 expression, in 9 of the 14 samples constitutively expressing cytokines, IL-6 transcript levels were elevated without a concomitant increase in IL-1 beta, suggesting that IL-6 transcription was independently dysregulated.
Department of Clinical Investigation, University of Texas M.D. Anderson Cancer Center, Houston.
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M
Wetzler
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R
Kurzrock
Z
Z
Estrov
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E
Estey
M
M
Talpaz
D000293:Adolescent; D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells; D002448:Cell Adhesion / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D016298:Hematopoietic Cell Growth Factors / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012016:Reference Values; D017154:Stromal Cells; D014158:Transcription, Genetic
D016207:Cytokines; D016298:Hematopoietic Cell Growth Factors; D007375:Interleukin-1; D009363:Neoplasm Proteins; D012333:RNA, Messenger