Targeting the bone marrow in Waldenstrom macroglobulinemia.
Waldenstrom macroglobulinemia (WM) is a low-grade B-cell lymphoma characterized by widespread involvement of the bone marrow with lymphoplasmacytic cells. In approximately 20% of patients, the malignant clone also involves the lymph nodes and induces hepatosplenomegaly. The mechanisms by which the tumor cells home to the bone marrow and preferentially reside in the marrow niches are not fully elucidated. In this review, we examine the role of the bone marrow microenvironment in the regulation of cell growth, survival and cell dissemination in WM. We also summarize specific regulators of niche-dependent tumor proliferation in WM. These include chemokines, adhesion molecules, Src/PI3K/Akt/mTOR signaling, NF-kB activation, and micro-RNA regulation in WM. Targeting these pathways in clinical trials could lead to significant responses in this rare disease.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. irene_ghobrial@dfci.harvard.edu
Irene M
IM
Ghobrial
Yong
Y
Zhang
Yang
Y
Liu
Hai
H
Ngo
Feda
F
Azab
Antonio
A
Sacco
Abdelkareem
A
Azab
Patricia
P
Maiso
Brittany
B
Morgan
Phong
P
Quang
Ghayas C
GC
Issa
Xavier
X
Leleu
Aldo M
AM
Roccaro
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D059016:Tumor Microenvironment; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*