The expression of cytokine and cytokine receptor genes in long-term bone marrow culture in congenital and acquired bone marrow hypoplasias.
A number of cytokines have been shown to have stimulatory activity on multipotent haematopoietic precursors. These include kit ligand (KL), interleukins (IL) 1, 3 and 6 and granulocyte macrophage-colony stimulating factor (GM-CSF). Using reverse transcriptase/polymerase chain reaction method (RT/PCR) we have examined the expression of these cytokines, the c-kit and IL-6 receptors, in long-term bone marrow culture (LTC) adherent layer cells in human bone marrow hypoplasia syndromes. Disorders studied include Fanconi's anaemia (FA, n = 16), idiopathic aplastic anaemia (AA, n = 11), Seckel's syndrome (n = 2), dyskeratosis congenita (n = 2), Shwachman-Diamond syndrome (n = 1), thrombocytopenia with absent radii syndrome (n = 1), acquired amegakaryocytosis (n = 1), paroxysmal nocturnal haemoglobinuria (n = 1) and acquired agranulocytosis (n = 1). IL-6 and GM-CSF expression appeared reduced in most patients with FA, suggesting that impaired production of these cytokines may contribute to the bone marrow failure seen in most patients with FA. In contrast, abundant IL-6 and GM-CSF expression were seen in most patients with AA when compared with the FA group and controls; these may be mediators of a stromal response in this disorder. No obvious differences were seen between the different patients' groups and controls in expression of the other cytokines or cytokine receptors studied.
Stark
R
R
Bone Marrow Transplant Unit, Hôpital Saint Louis, Paris, France.
Andre
C
C
Thierry
D
D
Cherel
M
M
Galibert
F
F
Gluckman
E
E
D000741:Anemia, Aplastic / Q000235:genetics; D001483:Base Sequence; D001853:Bone Marrow / Q000378:metabolism*; D001855:Bone Marrow Diseases / Q000151:congenital / Q000235:genetics*; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics*; D005199:Fanconi Anemia / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit; D012333:RNA, Messenger / Q000032:analysis; D011971:Receptors, Immunologic / Q000235:genetics*; D019947:Receptors, Interleukin-6; D013997:Time Factors
D016207:Cytokines; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D019009:Proto-Oncogene Proteins c-kit