Deregulation of innate immune and inflammatory signaling in myelodysplastic syndromes

I. Gañán-Gómez, Y. Wei, D. T. Starczynowski, S. Colla, H. Yang, M. Cabrero-Calvo, Z. S. Bohannan, Amit K. Verma, Ulrich G. Steidl, G. Garcia-Manero

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Myelodysplastic syndromes (MDSs) are a group of heterogeneous clonal hematologic malignancies that are characterized by defective bone marrow (BM) hematopoiesis and by the occurrence of intramedullary apoptosis. During the past decade, the identification of key genetic and epigenetic alterations in patients has improved our understanding of the pathophysiology of this disease. However, the specific molecular mechanisms leading to the pathogenesis of MDS have largely remained obscure. Recently, essential evidence supporting the direct role of innate immune abnormalities in MDS has been obtained, including the identification of multiple key regulators that are overexpressed or constitutively activated in BM hematopoietic stem and progenitor cells. Mounting experimental results indicate that the dysregulation of these molecules leads to abnormal hematopoiesis, unbalanced cell death and proliferation in patients' BM, and has an important role in the pathogenesis of MDS. Furthermore, there is compelling evidence that the deregulation of innate immune and inflammatory signaling also affects other cells from the immune system and the BM microenvironment, which establish aberrant associations with hematopoietic precursors and contribute to the MDS phenotype. Therefore, the deregulation of innate immune and inflammatory signaling should be considered as one of the driving forces in the pathogenesis of MDS. In this article, we review and update the advances in this field, summarizing the results from the most recent studies and discussing their clinical implications.

Original languageEnglish (US)
Pages (from-to)1458-1469
Number of pages12
JournalLeukemia
Volume29
Issue number7
DOIs
StatePublished - Jul 13 2015

Fingerprint

Myelodysplastic Syndromes
Bone Marrow
Hematopoiesis
Hematopoietic Stem Cells
Hematologic Neoplasms
Epigenomics
Immune System
Cell Death
Cell Proliferation
Apoptosis
Phenotype

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Gañán-Gómez, I., Wei, Y., Starczynowski, D. T., Colla, S., Yang, H., Cabrero-Calvo, M., ... Garcia-Manero, G. (2015). Deregulation of innate immune and inflammatory signaling in myelodysplastic syndromes. Leukemia, 29(7), 1458-1469. https://doi.org/10.1038/leu.2015.69

Deregulation of innate immune and inflammatory signaling in myelodysplastic syndromes. / Gañán-Gómez, I.; Wei, Y.; Starczynowski, D. T.; Colla, S.; Yang, H.; Cabrero-Calvo, M.; Bohannan, Z. S.; Verma, Amit K.; Steidl, Ulrich G.; Garcia-Manero, G.

In: Leukemia, Vol. 29, No. 7, 13.07.2015, p. 1458-1469.

Research output: Contribution to journalArticle

Gañán-Gómez, I, Wei, Y, Starczynowski, DT, Colla, S, Yang, H, Cabrero-Calvo, M, Bohannan, ZS, Verma, AK, Steidl, UG & Garcia-Manero, G 2015, 'Deregulation of innate immune and inflammatory signaling in myelodysplastic syndromes', Leukemia, vol. 29, no. 7, pp. 1458-1469. https://doi.org/10.1038/leu.2015.69
Gañán-Gómez I, Wei Y, Starczynowski DT, Colla S, Yang H, Cabrero-Calvo M et al. Deregulation of innate immune and inflammatory signaling in myelodysplastic syndromes. Leukemia. 2015 Jul 13;29(7):1458-1469. https://doi.org/10.1038/leu.2015.69
Gañán-Gómez, I. ; Wei, Y. ; Starczynowski, D. T. ; Colla, S. ; Yang, H. ; Cabrero-Calvo, M. ; Bohannan, Z. S. ; Verma, Amit K. ; Steidl, Ulrich G. ; Garcia-Manero, G. / Deregulation of innate immune and inflammatory signaling in myelodysplastic syndromes. In: Leukemia. 2015 ; Vol. 29, No. 7. pp. 1458-1469.
@article{8b880245030540a28ce14025c2e9dc94,
title = "Deregulation of innate immune and inflammatory signaling in myelodysplastic syndromes",
abstract = "Myelodysplastic syndromes (MDSs) are a group of heterogeneous clonal hematologic malignancies that are characterized by defective bone marrow (BM) hematopoiesis and by the occurrence of intramedullary apoptosis. During the past decade, the identification of key genetic and epigenetic alterations in patients has improved our understanding of the pathophysiology of this disease. However, the specific molecular mechanisms leading to the pathogenesis of MDS have largely remained obscure. Recently, essential evidence supporting the direct role of innate immune abnormalities in MDS has been obtained, including the identification of multiple key regulators that are overexpressed or constitutively activated in BM hematopoietic stem and progenitor cells. Mounting experimental results indicate that the dysregulation of these molecules leads to abnormal hematopoiesis, unbalanced cell death and proliferation in patients' BM, and has an important role in the pathogenesis of MDS. Furthermore, there is compelling evidence that the deregulation of innate immune and inflammatory signaling also affects other cells from the immune system and the BM microenvironment, which establish aberrant associations with hematopoietic precursors and contribute to the MDS phenotype. Therefore, the deregulation of innate immune and inflammatory signaling should be considered as one of the driving forces in the pathogenesis of MDS. In this article, we review and update the advances in this field, summarizing the results from the most recent studies and discussing their clinical implications.",
author = "I. Ga{\~n}{\'a}n-G{\'o}mez and Y. Wei and Starczynowski, {D. T.} and S. Colla and H. Yang and M. Cabrero-Calvo and Bohannan, {Z. S.} and Verma, {Amit K.} and Steidl, {Ulrich G.} and G. Garcia-Manero",
year = "2015",
month = "7",
day = "13",
doi = "10.1038/leu.2015.69",
language = "English (US)",
volume = "29",
pages = "1458--1469",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - Deregulation of innate immune and inflammatory signaling in myelodysplastic syndromes

AU - Gañán-Gómez, I.

AU - Wei, Y.

AU - Starczynowski, D. T.

AU - Colla, S.

AU - Yang, H.

AU - Cabrero-Calvo, M.

AU - Bohannan, Z. S.

AU - Verma, Amit K.

AU - Steidl, Ulrich G.

AU - Garcia-Manero, G.

PY - 2015/7/13

Y1 - 2015/7/13

N2 - Myelodysplastic syndromes (MDSs) are a group of heterogeneous clonal hematologic malignancies that are characterized by defective bone marrow (BM) hematopoiesis and by the occurrence of intramedullary apoptosis. During the past decade, the identification of key genetic and epigenetic alterations in patients has improved our understanding of the pathophysiology of this disease. However, the specific molecular mechanisms leading to the pathogenesis of MDS have largely remained obscure. Recently, essential evidence supporting the direct role of innate immune abnormalities in MDS has been obtained, including the identification of multiple key regulators that are overexpressed or constitutively activated in BM hematopoietic stem and progenitor cells. Mounting experimental results indicate that the dysregulation of these molecules leads to abnormal hematopoiesis, unbalanced cell death and proliferation in patients' BM, and has an important role in the pathogenesis of MDS. Furthermore, there is compelling evidence that the deregulation of innate immune and inflammatory signaling also affects other cells from the immune system and the BM microenvironment, which establish aberrant associations with hematopoietic precursors and contribute to the MDS phenotype. Therefore, the deregulation of innate immune and inflammatory signaling should be considered as one of the driving forces in the pathogenesis of MDS. In this article, we review and update the advances in this field, summarizing the results from the most recent studies and discussing their clinical implications.

AB - Myelodysplastic syndromes (MDSs) are a group of heterogeneous clonal hematologic malignancies that are characterized by defective bone marrow (BM) hematopoiesis and by the occurrence of intramedullary apoptosis. During the past decade, the identification of key genetic and epigenetic alterations in patients has improved our understanding of the pathophysiology of this disease. However, the specific molecular mechanisms leading to the pathogenesis of MDS have largely remained obscure. Recently, essential evidence supporting the direct role of innate immune abnormalities in MDS has been obtained, including the identification of multiple key regulators that are overexpressed or constitutively activated in BM hematopoietic stem and progenitor cells. Mounting experimental results indicate that the dysregulation of these molecules leads to abnormal hematopoiesis, unbalanced cell death and proliferation in patients' BM, and has an important role in the pathogenesis of MDS. Furthermore, there is compelling evidence that the deregulation of innate immune and inflammatory signaling also affects other cells from the immune system and the BM microenvironment, which establish aberrant associations with hematopoietic precursors and contribute to the MDS phenotype. Therefore, the deregulation of innate immune and inflammatory signaling should be considered as one of the driving forces in the pathogenesis of MDS. In this article, we review and update the advances in this field, summarizing the results from the most recent studies and discussing their clinical implications.

UR - http://www.scopus.com/inward/record.url?scp=84937023314&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84937023314&partnerID=8YFLogxK

U2 - 10.1038/leu.2015.69

DO - 10.1038/leu.2015.69

M3 - Article

VL - 29

SP - 1458

EP - 1469

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 7

ER -