UNIGE document Scientific Article
previous document  unige:79943  next document
add to browser collection
Title

Myelopoiesis dysregulation associated to sustained APRIL production in multiple myeloma-infiltrated bone marrow

Authors
Manfroi, B
Park, S
Published in Leukemia. 2015, vol. 29, no. 9, p. 1901-1908
Abstract Multiple myeloma (MM) is a non-curable tumor developing in the bone marrow (BM). The BM microenvironment rich in hematopoietic precursors is suspected to have a role in MM development. Here we show that a proliferation-inducing ligand (APRIL) mediated in vivo MM promotion. In MM-infiltrated BM, APRIL originated from differentiating myeloid cells with an expression peak in precursor cells. Notably, APRIL expression stayed stable in BM despite MM infiltration. The pool of APRIL-producing cells changed upon MM infiltration. Although CD16(+) mature myeloid cells constituted about half of the APRIL-producing cells in healthy BM, CD16(-) Elastase(+) myeloid precursor cells were predominant in MM-infiltrated BM. Myeloid precursor cells secreted all the APRIL they produced, and binding of secreted APRIL to MM cells, strictly dependent of heparan sulfate carried by CD138, resulted in an in situ internalization by tumor cells. This indicated APRIL consumption by MM in BM. Taken together, our data show that myelopoiesis dysregulation characterized by an increased proportion of precursor cells occurs in MM patients. Such dysregulation correlates with a stable expression of the MM-promoting factor APRIL in infiltrated BM.
Identifiers
PMID: 25753925
Full text
Article (Published version) (2.7 MB) - public document Free access
Structures
Research group Analyses cellulaires et moléculaires des hémopathies malignes (929)
Project Fondation Dr Dubois Ferrière /Dinu Lipatti
Citation
(ISO format)
MATTHES, Thomas et al. Myelopoiesis dysregulation associated to sustained APRIL production in multiple myeloma-infiltrated bone marrow. In: Leukemia, 2015, vol. 29, n° 9, p. 1901-1908. https://archive-ouverte.unige.ch/unige:79943

138 hits

57 downloads

Update

Deposited on : 2016-01-22

Export document
Format :
Citation style :