PMID- 38111584
OWN - NLM
STAT- MEDLINE
DCOM- 20231220
LR  - 20240403
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 14
DP  - 2023
TI  - AML alters bone marrow stromal cell osteogenic commitment via Notch signaling.
PG  - 1320497
LID - 10.3389/fimmu.2023.1320497 [doi]
LID - 1320497
AB  - INTRODUCTION: Acute myeloid leukemia (AML) is a highly heterogeneous malignancy 
      caused by various genetic alterations and characterized by the accumulation of 
      immature myeloid blasts in the bone marrow (BM). This abnormal growth of AML 
      cells disrupts normal hematopoiesis and alters the BM microenvironment 
      components, establishing a niche supportive of leukemogenesis. Bone marrow 
      stromal cells (BMSCs) play a pivotal role in giving rise to essential elements of 
      the BM niche, including adipocytes and osteogenic cells. Animal models have shown 
      that the BM microenvironment is significantly remodeled by AML cells, which skew 
      BMSCs toward an ineffective osteogenic differentiation with an accumulation of 
      osteoprogenitors. However, little is known about the mechanisms by which AML 
      cells affect osteogenesis. METHODS: We studied the effect of AML cells on the 
      osteogenic commitment of normal BMSCs, using a 2D co-culture system. RESULTS: We 
      found that AML cell lines and primary blasts, but not normal hematopoietic 
      CD34(+) cells, induced in BMSCs an ineffective osteogenic commitment, with an 
      increase of the early-osteogenic marker tissue non-specific alkaline phosphatase 
      (TNAP) in the absence of the late-osteogenic gene up-regulation. Moreover, the 
      direct interaction of AML cells and BMSCs was indispensable in influencing 
      osteogenic differentiation. Mechanistic studies identified a role for 
      AML-mediated Notch activation in BMSCs contributing to their ineffective 
      osteogenic commitment. Inhibition of Notch using a gamma-secretase inhibitor strongly 
      influenced Notch signaling in BMSCs and abrogated the AML-induced TNAP 
      up-regulation. DISCUSSION: Together, our data support the hypothesis that AML 
      infiltration produces a leukemia-supportive pre-osteoblast-rich niche in the BM, 
      which can be partially ascribed to AML-induced activation of Notch signaling in 
      BMSCs.
CI  - Copyright (c) 2023 Tomasoni, Arsuffi, Donsante, Corsi, Riminucci, Biondi, Pievani 
      and Serafini.
FAU - Tomasoni, Chiara
AU  - Tomasoni C
AD  - Tettamanti Center, Fondazione Istituto Ricovero e Cura a Carattere Scientifico 
      (IRCCS) San Gerardo dei Tintori, Monza, Italy.
FAU - Arsuffi, Corinne
AU  - Arsuffi C
AD  - Tettamanti Center, Fondazione Istituto Ricovero e Cura a Carattere Scientifico 
      (IRCCS) San Gerardo dei Tintori, Monza, Italy.
FAU - Donsante, Samantha
AU  - Donsante S
AD  - Tettamanti Center, Fondazione Istituto Ricovero e Cura a Carattere Scientifico 
      (IRCCS) San Gerardo dei Tintori, Monza, Italy.
AD  - Department of Molecular Medicine, Sapienza University, Rome, Italy.
FAU - Corsi, Alessandro
AU  - Corsi A
AD  - Department of Molecular Medicine, Sapienza University, Rome, Italy.
FAU - Riminucci, Mara
AU  - Riminucci M
AD  - Department of Molecular Medicine, Sapienza University, Rome, Italy.
FAU - Biondi, Andrea
AU  - Biondi A
AD  - Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
AD  - Pediatrics, Fondazione Istituto Ricovero e Cura a Carattere Scientifico (IRCCS) 
      San Gerardo dei Tintori, Monza, Italy.
FAU - Pievani, Alice
AU  - Pievani A
AD  - Tettamanti Center, Fondazione Istituto Ricovero e Cura a Carattere Scientifico 
      (IRCCS) San Gerardo dei Tintori, Monza, Italy.
FAU - Serafini, Marta
AU  - Serafini M
AD  - Tettamanti Center, Fondazione Istituto Ricovero e Cura a Carattere Scientifico 
      (IRCCS) San Gerardo dei Tintori, Monza, Italy.
AD  - Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
LA  - eng
PT  - Comment
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231204
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
SB  - IM
CON - Haematologica. 2021 Mar 01;106(3):865-870. PMID: 32381570
MH  - Animals
MH  - Osteogenesis
MH  - Bone Marrow Cells/metabolism
MH  - *Leukemia, Myeloid, Acute/pathology
MH  - Bone Marrow/metabolism
MH  - *Mesenchymal Stem Cells/metabolism
MH  - Tumor Microenvironment
PMC - PMC10725948
OTO - NOTNLM
OT  - AML niche
OT  - BMSCs (bone marrow stromal cells)
OT  - Notch signaling
OT  - acute myeloid leukemia
OT  - osteogenesis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/12/19 06:41
MHDA- 2023/12/20 06:42
PMCR- 2023/01/01
CRDT- 2023/12/19 03:51
PHST- 2023/10/12 00:00 [received]
PHST- 2023/11/20 00:00 [accepted]
PHST- 2023/12/20 06:42 [medline]
PHST- 2023/12/19 06:41 [pubmed]
PHST- 2023/12/19 03:51 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2023.1320497 [doi]
PST - epublish
SO  - Front Immunol. 2023 Dec 4;14:1320497. doi: 10.3389/fimmu.2023.1320497. 
      eCollection 2023.