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Molecular and cellular aspects of extramedullary manifestations of acute
myeloid leukemia

Javad Mohammadiasl , Abbas Khosravi , Mohammad Shahjahani , Shirin Azizidoost , Najmaldin Saki 2
2
2
1
2
1 Department of Medical Genetics, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 6135715794, Iran.
2 Health Research Institute, Research Center of Thalassemia and Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz
6135715794, Iran.
Correspondence to: Dr. Najmaldin Saki, Health Research Institute, Research Center of Thalassemia and Hemoglobinopathy, Ahvaz Jundishapur
University of Medical Sciences, Ahvaz 6135715794, Iran. E-mail: najmaldinsaki@gmail.com
A B S T R AC T
The myeloid extramedullary tumor is a solid tumor formed by infiltration of immature myeloid cells in various tissues of the
body. This tumor is also identified as chloroma or myeloid sarcoma (MS). MS is a manifestation of acute myeloid leukemia
(AML) occurring at presentation or during treatment or relapse. MS is associated with multiple chromosomal abnormalities and
molecular mutations since patients with these disorders bear a high potential for MS manifestation. There is a high incidence of
extramedullary infiltration (EMI) in AML. AML patients with EMI have a worse prognosis than patients without it. Hematopoietic
stem cells and leukemic stem cells reside in a special bone marrow microenvironment called niche, which is essential for their
normal functions. Cancers are exploited dysfunctional cell-cell and matrix-cell interactions, which convert a normal niche into a
neoplastic niche. This study summarizes the current knowledge on the molecular and cellular characteristics of AML with EMI
and extramedullary niches in AML patients.

Key words: Acute myeloid leukemia; extramedullary infiltration; niche

INTRODUCTION lining blood vessels, and it promotes the proliferation and
differentiation of short-term HSCs. The endosteal niche
Acute myeloid leukemia (AML) is an aggressive includes osteoblasts, osteoclasts, glial non-myelinating
myeloid neoplasm characterized by maturation arrest of Schwann cells and regulatory T-cells, and it is located in the
myelopoiesis leading to an accumulation of myeloblasts endosteum. The vascular niche contains CXCL12-abundant
in the blood and bone marrow (BM). AML is a complex reticular cells, nestin-positive mesenchymal stem cells
[1]
[4]
and heterogeneous disease strongly associated with genetic and leptin receptor-positive cells. HSC niches are present
and epigenetic changes in the hematopoietic progenitors. in different tissues during development, first in the aorta-
[2]
These changes lead to disruption of several signaling gonad-mesonephros (AGM) region and yolk sac, then in the
pathways that result in increased proliferation, survival and placenta, fetal liver, spleen and BM. After birth, the BM is
accumulation of leukemic cells. [3] the primary site of HSC maintenance and hematopoiesis,
but the niche can shift to extramedullary sites in response to
Normal hematopoietic stem cells (HSCs) reside in a hematopoietic stress. [5]
specialized area of the BM microenvironment known as
niche, which regulates their survival and function. Two AML may present with extramedullary-AML at initial
distinct niches exist in the BM: Vascular and endosteal/ diagnosis or in relapse. Myeloid sarcoma (MS) is defined
osteoblastic niche. The vascular niche is localized in close as an extramedullary mass composed of myeloid blasts
[6]
proximity to the osteoblastic niche, at the inner surface of occurring in anatomic sites other than BM. Extramedullary
bone cavity with abundant bone-forming osteoblasts. The
vascular niche is composed of sinusoidal endothelial cells This is an open access article distributed under the terms of the Creative
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How to cite this article: Mohammadiasl J, Khosravi A, Shahjahani M,
Azizidoost S, Saki N. Molecular and cellular aspects of extramedullary
manifestations of acute myeloid leukemia. J Cancer Metastasis Treat
DOI: 2016;2:44-50.
10.4103/2394-4722.167230
Received: 01-02-2015; Accepted: 09-09-2015.

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© 2016 Journal of Cancer Metastasis and Treatment ¦ Published by OAE Publishing Inc.