Immune Dysregulation in Myelodysplastic Syndrome

Overview

Journal Hematol Rep

Publisher MDPI

Date 2011 Dec 21

PMID 22184512

Citations 8

Authors

Chiharu Sugimori

Alan F List

Pearlie K Epling-Burnette

Affiliations

Soon will be listed here.

Abstract

Myelodysplastic syndrome (MDS) represents one of the most challenging health-related problems in the elderly. Characterized by dysplastic morphology in the bone marrow in association with ineffective hematopoiesis, pathophysiological causes of this disease are diverse including genetic abnormalities within myeloid progenitors, altered epigenetics, and changes in the bone marrow microenvironment. The concept that T-cell mediated autoimmunity contributes to bone marrow failure has been widely accepted due to hematologic improvement after immunosuppressive therapy (IST) in a subset of patients. Currently, IST for MDS primarily involves anti-thymocyte globulin (ATG)-based regimens in which responsiveness is strongly associated with younger (under 60 years) age at disease onset. In such cases, progressive cytopenia may occur as a consequence of expanded self-reactive CD8(+) cytotoxic T lymphocytes (CTLs) that suppress hematopoietic progenitors. Although most hematologists agree that IST can offer durable hematologic remission in younger patients with MDS, an international clinical study and a better understanding of the molecular mechanisms contributing to the expansion of self-reactive CTLs is crucial. In this review, data accumulated in the US, Europe, and Asia will be summarized to provide insight and direction for a multi-center international trial.

Citing Articles

Bone Marrow Immune Microenvironment in Myelodysplastic Syndromes.

Kouroukli O, Symeonidis A, Foukas P, Maragkou M, Kourea E Cancers (Basel). 2022; 14(22).

PMID: 36428749 PMC: 9688609. DOI: 10.3390/cancers14225656.

Comparative study of IgG binding to megakaryocytes in immune and myelodysplastic thrombocytopenic patients.

Elzaeem D, Sharkawi E, Zaki E, Ghobrial A, El-Fatah A, El-Hamed W Ann Hematol. 2021; 100(7):1701-1709.

PMID: 33982136 DOI: 10.1007/s00277-021-04556-2.

High mutation burden in the checkpoint and micro-RNA processing genes in myelodysplastic syndrome.

Moiseev I, Tcvetkov N, Barkhatov I, Barabanshikova M, Bug D, Petuhova N PLoS One. 2021; 16(3):e0248430.

PMID: 33730109 PMC: 7968630. DOI: 10.1371/journal.pone.0248430.

Frequent mutations in CD8 T cells from patients with pure red cell aplasia.

Kawakami T, Sekiguchi N, Kobayashi J, Imi T, Matsuda K, Yamane T Blood Adv. 2018; 2(20):2704-2712.

PMID: 30337298 PMC: 6199660. DOI: 10.1182/bloodadvances.2018022723.

CD8 T cells drive autoimmune hematopoietic stem cell dysfunction and bone marrow failure.

Gravano D, Al-Kuhlani M, Davini D, Sanders P, Manilay J, Hoyer K J Autoimmun. 2016; 75:58-67.

PMID: 27453063 PMC: 5121063. DOI: 10.1016/j.jaut.2016.07.007.

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