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The Bone Marrow Niche – The Tumor Microenvironment That Ensures Leukemia Progression

  • Bruno António CardosoEmail author
Chapter
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Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1219)

Abstract

The human body requires a constant delivery of fresh blood cells that are needed to maintain body homeostasis. Hematopoiesis is the process that drives the formation of new blood cells from a single stem cell. This is a complex, orchestrated and tightly regulated process that occurs within the bone marrow. When such process is faulty or deregulated, leukemia arises, develops and thrives by subverting normal hematopoiesis and availing the supplies of this rich milieu.

In this book chapter we will describe and characterize the bone marrow microenvironment and its key importance for leukemia expansion. The several components of the bone marrow niche, their interaction with the leukemic cells and the cellular pathways activated within the malignant cells will be emphasized. Finally, novel therapeutic strategies to target this sibling interaction will also be discussed.

Keywords

Hematopoiesis Leukemia Bone marrow Microenvironment Signaling pathways Dual-targeting 

Abbreviations

PDK

3-Phosphinositide-dependent Protein Kinase

Ang

Angiopoietin

AGM

Aorta-gonad-mesonephros

ALL

Acute Lymphoblastic Leukemia

AML

Acute Myeloid Leukemia

B-ALL

B-cell Acute Lymphoblastic Leukemia

BM

Bone Marrow

BMP

Bone Morphogenetic Protein

CNS

Central Nervous System

CML

Chronic Myeloid Leukemia

CSF

Colony-stimulating Factor

CLP

Common Lymphoid Progenitor

CMP

Common Myeloid Progenitor

CAR

CXCL12 Abundant Reticular cells

CXCR4

C-X-C chemokine receptor 4

CXCL12

C-X-C motif chemokine ligand 12

Ara-C

Cytarabine

Dll-1

Delta-like-1

DHH

Desert Hedgehog

ETP-ALL

Early T-cell Precursor Acute Lymphoblastic Leukemia

EC

Endothelial Cells

ECM

Extracellular Matrix

FABP4

Fatty Acid Binding Protein 4

FAO

Fatty Acid Oxidation

FGF

Fibroblast Growht Factor

FL

Fetal Liver

GAL

Galectin

GMP

Granulocyte-monocyte Progenitors

G-CSF

Granulocyte-stimulating factor

GLI

Glioma Zinc Finger Transcription Factor

HSC

Hematopoietic Stem Cell

HIF

Hypoxia Inducible Factor

IHH

Indian Hedgehog

IFN

Interferon

IGFBP

Insulin-like Growth Factor Binding Protein

IL

Interleukin

ICAM-1

Intracellular Adhesion Molecule-1

ICN

Intracellular Notch

JAK

Janus kinase

LepR

Leptin receptor

LIC

Leukemia Initiating Cell

LSC

Leukemic Stem Cell

LSK

Lin Sca-1+ c-Kit+

LT-HSC

Long-Term Hematopoietic Stem Cell

LFA-1

Lymphocyte Function Associated Antigen-1

mTOR

Mammalian Target of Rapamycin

MEP

Megakaryocyte-erythrocyte Progenitors

MSC

Mesenchymal Stem Cell

OB

Osteoblast

OC

Osteoclast

OPN

Osteopontin

PDX

Patient-derived Xenograft

PTEN

Phosphatase and Tensin Homologue

PIP2

Phosphatidyl-Inositol 4,5-Bisphosphate

PIP3

Phosphatidyl-Inositol 3,4,5-Trisphosphate

PI3K

Phospho-Inositol-3-Kinase

PKB/Akt

Protein Kinase B

RBC

Red Blood Cell

ST-HSC

Short-Term Hematopoietic Stem Cell

STAT

Signal Transducer and Activator of Transcription

SMO

Smoothened

SHH

Sonic Hedgehog

SCF

Stem Cell Factor

SC

Stromal Cell

SDF-1

Stromal Derived Factor -1

SNC

Sympathetic neural cells

T-ALL

T-cell Acute Lymphoblastic Leukemia

TCF/LEF

T-cell factor/Lymphoid enhancer binding factor

TGF

Transforming Growth Factor

TPO

Thrombopoietin

TNF

Tumor Necrosis Factor

TKI

Tyrosine Kinase Inhibitor

VCAM-1

Vascular Cell Adhesion Molecule-1

VE

Vascular Endothelial

VEGF

Vascular Endothelial Growth Factor

VEGFR

Vascular Endothelial Growth Factor Receptor

VLA-4

Very Late Antigen-4

VHL

von Hippel-Lindau

WNT

Wingless and INT-1

WHO

World Health Organization

YS

Yolk-Sac

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Instituto de Medicina Molecular João Lobo AntunesFaculdade de Medicina da Universidade de LisboaLisbonPortugal

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