PMID- 29358175
OWN - NLM
STAT- MEDLINE
DCOM- 20190514
LR  - 20210202
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 131
IP  - 15
DP  - 2018 Apr 12
TI  - Extracellular vesicle-mediated transfer of constitutively active MyD88(L265P) 
      engages MyD88(wt) and activates signaling.
PG  - 1720-1729
LID - 10.1182/blood-2017-09-805499 [doi]
AB  - The link between inflammation and cancer is particularly strong in Waldenstrom 
      macroglobulinemia (WM), a diffuse large B-cell lymphoma wherein the majority of 
      patients harbor a constitutively active mutation in the innate immune-signaling 
      adaptor myeloid differentiation primary response 88 (MyD88). MyD88Leu265Pro 
      (MyD88(L265P)) constitutively triggers the myddosome assembly providing a 
      survival signal for cancer cells. Here, we report detection and a functional role 
      of MyD88 in the extracellular vesicles (EVs) shed from WM cells. MyD88(L265P) was 
      transferred via EVs into the cytoplasm of the recipient mast cells and 
      macrophages, recruiting the endogenous MyD88 that triggered the activation of 
      proinflammatory signaling in the absence of receptor activation. Additionally, 
      internalization of EVs containing MyD88(L265P) was observed in mice with an 
      effect on the bone marrow microenvironment. MyD88-loaded EVs were detected in the 
      bone marrow aspirates of WM patients thus establishing the physiological role of 
      EVs for MyD88(L265P) transmission and shaping of the proinflammatory 
      microenvironment. Results establish the mechanism of transmission of signaling 
      complexes via EVs to propagate inflammation as a new mechanism of intercellular 
      communication.
CI  - (c) 2018 by The American Society of Hematology.
FAU - Mancek-Keber, Mateja
AU  - Mancek-Keber M
AD  - Department of Synthetic Biology and Immunology, National Institute of Chemistry, 
      Ljubljana, Slovenia.
FAU - Lainscek, Dusko
AU  - Lainscek D
AD  - Department of Synthetic Biology and Immunology, National Institute of Chemistry, 
      Ljubljana, Slovenia.
FAU - Bencina, Mojca
AU  - Bencina M
AD  - Department of Synthetic Biology and Immunology, National Institute of Chemistry, 
      Ljubljana, Slovenia.
AD  - EN-FIST Centre of Excellence, Ljubljana, Slovenia.
FAU - Chen, Jiaji G
AU  - Chen JG
AUID- ORCID: 0000-0001-6393-6154
AD  - Bing Center for Waldenstrom's Macroglobulinemia, Dana-Farber Cancer Institute, 
      Boston, MA.
AD  - Department of Medicine, Harvard Medical School, Boston, MA; and.
FAU - Romih, Rok
AU  - Romih R
AD  - Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, 
      Ljubljana, Slovenia.
FAU - Hunter, Zachary R
AU  - Hunter ZR
AUID- ORCID: 0000-0002-1689-1691
AD  - Bing Center for Waldenstrom's Macroglobulinemia, Dana-Farber Cancer Institute, 
      Boston, MA.
AD  - Department of Medicine, Harvard Medical School, Boston, MA; and.
FAU - Treon, Steven P
AU  - Treon SP
AUID- ORCID: 0000-0001-6393-6154
AD  - Bing Center for Waldenstrom's Macroglobulinemia, Dana-Farber Cancer Institute, 
      Boston, MA.
AD  - Department of Medicine, Harvard Medical School, Boston, MA; and.
FAU - Jerala, Roman
AU  - Jerala R
AUID- ORCID: 0000-0002-6337-5251
AD  - Department of Synthetic Biology and Immunology, National Institute of Chemistry, 
      Ljubljana, Slovenia.
AD  - EN-FIST Centre of Excellence, Ljubljana, Slovenia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180122
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
SB  - IM
CIN - Blood. 2018 Apr 12;131(15):1635-1636. PMID: 29650731
MH  - Amino Acid Substitution
MH  - Animals
MH  - Bone Marrow/*metabolism/pathology
MH  - *Cell Communication
MH  - Extracellular Vesicles/genetics/*metabolism/pathology
MH  - Female
MH  - HEK293 Cells
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Transgenic
MH  - *Mutation, Missense
MH  - Myeloid Differentiation Factor 88/genetics/*metabolism
MH  - *Signal Transduction
MH  - Waldenstrom Macroglobulinemia/genetics/*metabolism/pathology
EDAT- 2018/01/24 06:00
MHDA- 2019/05/15 06:00
CRDT- 2018/01/24 06:00
PHST- 2017/09/07 00:00 [received]
PHST- 2018/01/13 00:00 [accepted]
PHST- 2018/01/24 06:00 [pubmed]
PHST- 2019/05/15 06:00 [medline]
PHST- 2018/01/24 06:00 [entrez]
AID - S0006-4971(20)32322-3 [pii]
AID - 10.1182/blood-2017-09-805499 [doi]
PST - ppublish
SO  - Blood. 2018 Apr 12;131(15):1720-1729. doi: 10.1182/blood-2017-09-805499. Epub 
      2018 Jan 22.