Concise Review: Adaptation of the Bone Marrow Stroma in Hematopoietic Malignancies: Current Concepts and Models

Abstract

The bone marrow stroma maintains hematopoiesis and coordinately regulates regenerative responses through dynamic interactions with hematopoietic stem and progenitor cells. Recent studies indicate that stromal components in the bone marrow of leukemia patients undergo a process of successive adaptation that in turn exerts dramatic effects on the hematopoietic stem cell compartment and promotes leukemic drug resistance. Therefore, functional changes in discrete marrow stromal populations can be considered an aspect of leukemia biogenesis in that they create an aberrant, self-reinforcing microenvironment. In this review, we will describe the current understanding of the remodeling of the hematopoietic stem cell niche following invasion by leukemia cells. We place emphasis on existing evidence of how mesenchymal stem cells and their progeny facilitate neoplastic growth and describe available models and analytical techniques to understand the conversion of the niche toward disease persistence. STEM CELLS 2018;36:304-312 SIGNIFICANCE STATEMENTThere is increasing awareness that the bone marrow microenvironment is a critical contributor to therapeutic resistance and relapse progression in hematological malignancies. Experimental evidence discussed herein highlights key aspects of the stromal conversion by leukemia and the resulting aberrant signaling within the niche. This article discusses the advantages and limitations of available experimental model system and emphasizes open scientific questions and opportunities.

Expression of the Immune Checkpoint Modulator OX40 in Acute Lymphoblastic Leukemia Is Associated with BCR-ABL Positivity

“…It seems thus possible that OX40 confers a survival benefit for leukemic cells, e.g., upon interaction with OX40L bearing immune or bystander cells. This is in line with increasing evidence regarding the important role of the immune and stromal microenvironment in malignancies [38] .…”

Approaches to mimic the complexity of the skeletal mesenchymal stem/stromal cell niche in vitro

“…MSC and their progeny may facilitate neoplastic growth (Doron et al, 2018). Communication between MSCs and bone-metastatic DCCs is unclear, but it is possible that MSCs control DCC settlement in the BM as competition for niche space may exist (Dhawan et al, 2016;Gordon et al, 2014;Rossnagl et al, 2018;Shiozawa et al, 2015).…”

The Influence of the Environmental Environment on the State of Hemopoesis and the Development and Course of Acute Leukemia in Children after the Chernobil Catastrophe

“…Відомо, що строма кісткового мозку впливає на гемопоез і координує взаємодію з клітинами-попередниками [8,9,10]. Зокрема, стромальні фібробласти формують гемопоетичне мікрооточення і можуть відігравати як захисну роль, так і бути промоторами пухлинного процесу [11].…”