RESUMEN
Immunomodulation is a mechanism that stimulates or inhibits immune responses under the influence of secretory mediators. This study will review the role of cytokines and chemotherapy in the modulation of immune responses in leukemia. We searched the PubMed database and Google scholar search engine of English-language papers (1995-2018) using the "Immunomodulation", "Leukemia", "Tregs", "Natural killer cells", "Mesenchymal stem cells", "Macrophages" and "chemotherapy" as keywords. In leukemias, T regulatory cells (Tregs), natural killer cells (NK), macrophages (MQs) and mesenchymal stem cells (MSCs) alter their functional and secretion patterns. Some of the changes in NK cells and classic MQ (M1) potentiate the immune responses against leukemia, but some Tregs changes will compromise the immune system. The effect of a cell on immunomodulation is in contrast to another cell, in which the cells are engaged in a competition so that a cell that having a higher effect on immunomodulation will be the contest winner. The outcome of immunomodulation in response to leukemia is determined by the ratio of stimulatory activity of NK cells and M1 to the inhibitory effect of Tregs, while the dual role of MSCs through immunomodulators and cytokines can be effective in weakening/enhancing the immune response.
Asunto(s)
Antineoplásicos/uso terapéutico , Citocinas/metabolismo , Inmunomodulación/inmunología , Células Asesinas Naturales/inmunología , Leucemia/inmunología , Linfocitos T Reguladores/inmunología , Humanos , Inmunomodulación/efectos de los fármacos , Leucemia/tratamiento farmacológico , Leucemia/metabolismo , Leucemia/patologíaRESUMEN
Despite significant progress in the treatment of different types of leukemia, relapse remains a challenging clinical problem that is observed in a number of patients who are often resistant to chemotherapy and exhibit multi-drug resistance. Identification of new functional biomarkers, including microRNAs, is essential to determine prognosis and relapse at the time of diagnosis. The aim of this study was to detect the specific microRNAs involved in predicting relapse or progression in acute and chronic leukemias, as well as their relationship with overall survival (OS) and relapse-free survival (RFS). The relevant literature was identified through a PubMed and Scholar search (2008-2016) of English-language papers using the terms Leukemia, microRNAs, survival and relapse. Different leukemia types and subtypes show specific microRNA expression profile and different changes, which can be useful in the differentiation between leukemias and evaluation of relapse at the time of diagnosis. Altered microRNA expression profiles can turn these molecules into oncogenes or tumor suppressors, which affect the expression of relapse-related genes. Therefore, monitoring of specific microRNA expression profiles from diagnosis and during follow-up of patients can contribute to the assessment of outcome and determination of relapse and prognosis of leukemic patients.
Asunto(s)
Biomarcadores de Tumor/genética , Leucemia/terapia , MicroARNs/genética , Recurrencia Local de Neoplasia/diagnóstico , Terapia Combinada , Humanos , Leucemia/genética , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/genética , PronósticoRESUMEN
Osteoblasts are one among the critical components of the endosteal bone marrow (BM) niche. In addition to hematopoietic stem cell fate, their role in leukemogenesis as well as metastasis of a variety of cancers has been demonstrated in various studies. In this regard, endosteal niche can have a dual role as an initiator and protective role against leukemia. Knowledge of growth factors, chemokines and cytokines secreted by osteoblasts as well as their interaction with signaling pathways inform our understanding of the development, prognosis, recurrence and treatment of malignant BM diseases. Clinical progress in targeting the endosteal niche is also discussed.
Asunto(s)
Médula Ósea/patología , Transformación Celular Neoplásica/patología , Leucemia/patología , Osteoblastos/patología , Nicho de Células Madre/fisiología , Animales , HumanosRESUMEN
BACKGROUND: Essential thrombocythemia (ET) is a benign disease with slow progress in which thrombosis is a cause of mortality. JAK2V617F and calreticulin (CALR) are the most frequent mutations in this disease. In this systematic review and meta-analysis, we compared the prevalence of JAK2V617F and CALR mutations in ET and examined the incidence of thrombosis and other hematologic indices. METHODS: After choosing MeSH keywords, including essential thrombocythemia, JAK2V617F, calreticulin, prognosis, and diagnosis, as well as searching Medline/PubMed and Scopus, 12 papers were selected. Data were pooled, and summary prevalence and OR were estimated using either a random-effects model or a fixed-effects model. RESULTS: The frequency of JAK2V617F and CALR shows heterogeneity in Caucasian population [JAK2V617 I 2% = 84.3, P < 0.001, 95% CI 0.56 (0.51-0.61)], [CALR I 2% = 96.1, P < 0.001, 95% CI 0.23 (0.15-0.31)]. The prevalence of JAK2V617F and CALR was 0.57 (95% CI 0.53-0.61), I 2% = 79.3 and 0.22 (95% CI 0.16-0.27), I 2% = 94, respectively. JAK2V617F positive ET was associated with increasing odds of thrombosis [OR 2.35 (95% CI 1.83-3.02), P < 0.001]. The incidence of splenomegaly was not statistically different between these two mutations. Hemoglobin, platelet, and WBC count did not affect the risk of thrombosis. CONCLUSIONS: Detection of CALR mutation is helpful for molecular diagnosis of ET patients as well as JAK2V617F. Due to reduction of thrombosis in CALR-positive patients, it can be stated that such patients have less thrombotic disorders and better prognosis relative to patients bearing JAK2V617F mutation. Therefore, detection of mutation in CALR and JAK2V617F may contribute to diagnosis and prognosis of ET patients.
Asunto(s)
Calreticulina/genética , Janus Quinasa 2/genética , Mutación , Trombocitemia Esencial/diagnóstico , Trombocitemia Esencial/genética , Humanos , PronósticoRESUMEN
Angiogenesis, the process of blood vessel formation, is necessary for tissue survival in normal and pathologic conditions. Increased angiogenesis in BM niche is correlated with leukemia progression and resistance to treatment. Angiogenesis can interfere with disease progression and several angiogenic (such as vascular growth factors) as well as anti-angiogenic factors (i.e. angiostatin) can affect angiogenesis. Furthermore, miRs can affect the angiogenic process by inhibiting angiogenesis or increasing the expression of growth factors. Given the importance of angiogenesis in BM for maintenance of leukemic clones, recognition of angiogenic and anti-angiogenic factors and miRs as well as drug resistance mechanisms of leukemic blasts can improve the therapeutic strategies. We highlight the changes in angiogenic balance within the BM niche in different leukemia types. Moreover, we explored the pathways leading to drug resistance in relation to angiogenesis and attempted to assign interesting candidates for future research.
Asunto(s)
Médula Ósea/irrigación sanguínea , Leucemia/fisiopatología , Neovascularización Patológica , Animales , Humanos , Transducción de SeñalRESUMEN
Central nervous system (CNS) impairment is commonly involved in leukemia, as it can be observed upon onset or relapse of the disease. It is associated with poor prognosis and is a challenging clinical problem. The objective of this paper was to provide a characterization of the CNS niche in leukemia, to elucidate the culprits of CNS involvement, including diagnostic micro RNAs (miRs) and early leukemia prognosis. CNS niche is a proper location for homing of leukemic stem cells, thus representing a candidate target in the treatment of leukemia. Recent advances in the study of leukemia hallmarks have enlightened miRs as novel biomarkers for diagnosis and detection of CNS involvement in leukemia, thus providing the opportunity to develop novel therapeutic approaches. Given the importance of prognosis and early diagnosis of CNS involvement in leukemias as well as the severe side effects of current treatments, diagnostic and therapeutic approaches should focus on identification and inhibition of the factors contributing to CNS involvement, including CXCR3, P-selectin glycoprotein ligand-1 and MCP1. MiRs such as miR-221 and miR-222 are emerging as potential tools for an innovative non-invasive therapy of CNS in leukemia affected patients.
Asunto(s)
Neoplasias del Sistema Nervioso Central/patología , Leucemia/patología , Células Madre Neoplásicas/patología , Nicho de Células Madre , Movimiento Celular , HumanosRESUMEN
Twist proteins are members of basic helix-loop-helix family and are major regulators of embryogenesis. In adult humans, Twist proteins are mainly expressed in precursor cells, including myogenic, osteoblastic, chondroblastic and myelomonocytic lineages, maintaining their undifferentiated state. In addition, they play important roles in lymphocyte function and maturation. Recently, several studies have reported regulatory roles for Twist in the function and development of hematopoietic cells as well as in survival and development of numerous hematological malignancies. It is activated by numerous signal transduction pathways, including Akt, nuclear factor κB, Wnt, signal transducer and activator of transcription 3, mitogen-activated protein kinase and Ras signaling. Activated Twist has an anti-apoptotic role and protects cancer cells from apoptotic cell death. In addition, overexpression of Twist promotes the process of epithelial-mesenchymal transition, which has an essential role in cancer metastasis. Hereby, we review the aberrant expression of Twist in hematopoietic malignancies such as leukemias, lymphomas and myelodysplastic syndrome, which is related with poor prognosis and drug resistance in these disorders. Inactivation of Twist by small RNAs technology or chemotherapeutic inhibitors targeting Twist and upstream or downstream molecules of Twist signaling pathways may be helpful in management of disease to improve treatment strategies in malignancies.