Premium
Interleukin‐11 (IL‐11) acts as a synergistic factor for the proliferation of human myeloid leukaemic cells
Author(s) -
Lemoli Roberto M.,
Fogli Miriam,
Fortuna Alessandra,
Amabile Marilina,
Zucchini Patrizia,
Grande Alexis,
Martinelli Giovanni,
Visani Giuseppe,
Ferrari Sergio,
Tura Sante
Publication year - 1995
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1995.tb05296.x
Subject(s) - clonogenic assay , cytokine , stem cell factor , haematopoiesis , progenitor cell , interleukin 3 , myeloid , biology , microbiology and biotechnology , cell culture , growth factor , granulocyte macrophage colony stimulating factor , stem cell , cancer research , immunology , receptor , t cell , antigen presenting cell , biochemistry , immune system , genetics
Summary. Interleukin‐11 is a stromal cells derived cytokine which stimulates the proliferation of primitive haemopoietic progenitor cells. For this paper we have studied the constitutive expression of IL‐11 mRNA in a panel of well‐known leukaemic cell lines and samples from AML patients at diagnosis. Moreover, the same cellular populations were evaluated for their proliferative response to recombinant‐human‐(r‐hu) IL‐11 alone and combined with r‐hu‐IL‐3, granulocyte‐macrophage colony stimulating factor (GM‐CSF) and stem cell factor (SCF, c‐kit ligand). The colony‐forming ability of HL60, K562, KG1 cells and eight fresh AML cell populations was assessed by a clonogenic assay in methylcellulose. In eight additional AML cases the number of S‐phase leukaemic cells induced by IL‐11 was determined by the bromodeoxyuridine (BRDU) incorporation assay after 3 d of liquid culture. IL‐11, as single cytokine, did not stimulate the colony formation of the three myeloid cell lines under serum‐containing and serum‐free conditions. In contrast, the proliferation of the leukaemic cells in response to IL‐3, GM‐CSF and SCF was enhanced by co‐incubation with IL‐11, and this effect was reversed in blocking experiments by the anti‐IL‐11 Moab. When tested on primary AML samples, IL‐11 alone showed little, if any, proliferative activity. However, it increased the IL‐3‐dependent blast colony formation in eight out of eight cases and GM‐CSF in seven cases. IL‐11 also augmented synergistically the number of CFU‐L stimulated by SCF in seven cases. A combination of three factors (IL‐11, SCF and IL‐3) yielded optimal colony formation. The BRDU studies showed the significant increase of AML cells in S‐phase when IL‐11 was combined with SCF, whereas the two CSF had no activity on their own. Positive interaction was also observed when IL‐11 was added to IL‐3 supplemented cultures in five out of eight cases tested. Reverse transcriptase‐polymerase chain reaction amplification (RT‐PCR) demonstrated the constitutive expression of IL‐11 mRNA in all the cell lines and 11/12 AML samples studied at diagnosis. These results indicate that IL‐11 is expressed in leukaemic myeloid cells and that their proliferation is regulated by the cytokine which acts as a synergistic factor.