Targeting the PI3K/Akt/mTOR pathway may have pro-apoptotic and antiproliferative effects on hematological malignancies. Furthermore, modulation of miRNA can be used as a novel therapeutic approach to regulate the PI3K/Akt/mTOR pathway. However, both aspects require further clinical studies.

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Tumor cells are able to attract mesenchymal stem cells (MSCs) to primary tumor site. On the other hand, MSCs secrete various factors to attract tumor cells towards BM. In this review, in addition to assessment of MSCs function at tumor sites and their impact on growth and metastasis of tumor cells, the importance of MSC in attraction of malignant cells to BM and their involvement in drug resistance of tumor cells have also been studied. Relevant literature was identified by a PubMed search (2000-2015) of English-language literature using the terms mesenchymal stem cells, cancer cell, metastasis, and tumor microenvironment. MSCs migrate towards tumor microenvironment and are involved in both pro-tumorigenic and antitumorigenic functions. The dual function of MSCs at tumor sites is dependent upon a variety of factors, including the type and origin of MSCs, the cancer cell line under study, in vivo or in vitro conditions, the factors secreted by MSCs and interactions between MSCs, host immune cells and cancer cells. Therefore, MSCs can be regarded both as friends and enemies of cancer cells. Although the role of a number of pathways, including IL-6/STAT3 pathway, has been indicated in controlling the interaction between MSCs and tumor cells, other mechanisms by which MSCs can control the tumor cells are not clear yet. A better understanding of these mechanisms through further studies can determine the exact role of MSCs in cancer progression and identify them as important therapeutic agents or targets.

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by increased bleeding tendency and thrombocytopenia. In fact, the precise pathogenesis of this disease is still not clear. Megakaryopoiesis involves complete differentiation of megakaryocyte (MK) progenitors to functional platelets. This complex process occurs in specific bone marrow (BM) niches composed of several hematopoietic and non-hematopoietic cell types, soluble factors, and extracellular matrix proteins. These specialized microenvironments sustain MK maturation and localization to sinusoids as well as platelet release into circulation. However, MKs in ITP patients show impaired maturation and signs of degradation. Intrinsic defects in MKs and their extrinsic environment have been implicated in altered megakaryopoiesis in this disease. In particular, aberrant expression of miRNAs directing MK proliferation, differentiation, and platelet production; defective MK apoptosis; and reduced proliferation and differentiation rate of the MSC compartment observed in these patients may account for BM defects in ITP. Furthermore, insufficient production of thrombopoietin is another likely reason for ITP development. Therefore, identifying the signaling pathways and transcription factors influencing the interaction between MKs and BM niche in ITP patients will contribute to increased platelet production in order to prevent incomplete MK maturation and destruction as well as BM fibrosis and apoptosis in ITP. In this review, we will examine the interaction and role of BM niches in orchestrating megakaryopoiesis in ITP patients and discuss how these factors can be exploited to improve the quality of patient treatment and prognosis.