Molecular Convergence in Ex Vivo Models of Diamond-Blackfan Anemia

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2017 Apr 6

PMID 28377399

Citations 21

Authors

Kelly A OBrien

Jason E Farrar

Adrianna Vlachos

Stacie M Anderson

Crystiana A Tsujiura

Jens Lichtenberg

Lionel Blanc

Eva Atsidaftos

Abdel Elkahloun

Xiuli An

Steven R Ellis

Jeffrey M Lipton

David M Bodine

Affiliations

Soon will be listed here.

Abstract

Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome characterized by erythroid hypoplasia, usually without perturbation of other hematopoietic lineages. Approximately 65% of DBA patients with autosomal dominant inheritance have heterozygous mutations or deletions in ribosomal protein (RP) genes while <1% of patients with X-linked inheritance have been identified with mutations in the transcription factor Erythroid cells from patients with DBA have not been well characterized, and the mechanisms underlying the erythroid specific effects of either RP or associated DBA remain unclear. We have developed an ex vivo culture system to expand peripheral blood CD34 progenitor cells from patients with DBA and differentiate them into erythroid cells. Cells from patients with RP or mutations showed decreased proliferation and delayed erythroid differentiation in comparison with controls. RNA transcript analyses of erythroid cells from controls and patients with RP or mutations showed distinctive differences, with upregulation of heme biosynthesis genes prominently in RP-mediated DBA and failure to upregulate components of the translational apparatus in -mediated DBA. Our data show that dysregulation of translation is a common feature of DBA caused by both RP and mutations. This trial was registered at www.clinicaltrials.gov as #NCT00106015.

Citing Articles

An RPS19-edited model for Diamond-Blackfan anemia reveals TP53-dependent impairment of hematopoietic stem cell activity.

Bhoopalan S, Yen J, Mayuranathan T, Mayberry K, Yao Y, Lillo Osuna M JCI Insight. 2022; 8(1).

PMID: 36413407 PMC: 9870085. DOI: 10.1172/jci.insight.161810.

Proerythroblast Cells of Diamond-Blackfan Anemia Patients With and Mutations Have Similar Transcriptomic Signature.

Karaosmanoglu B, Kursunel M, Uckan Cetinkaya D, Gumruk F, Esendagli G, Unal S Front Physiol. 2021; 12:679919.

PMID: 34177624 PMC: 8226250. DOI: 10.3389/fphys.2021.679919.

Direct Generation of Immortalized Erythroid Progenitor Cell Lines from Peripheral Blood Mononuclear Cells.

Bagchi A, Nath A, Thamodaran V, Ijee S, Palani D, Rajendiran V Cells. 2021; 10(3).

PMID: 33804564 PMC: 7999632. DOI: 10.3390/cells10030523.

Recapitulation of erythropoiesis in congenital dyserythropoietic anaemia type I (CDA-I) identifies defects in differentiation and nucleolar abnormalities.

Scott C, Downes D, Brown J, Beagrie R, Olijnik A, Gosden M Haematologica. 2020; 106(11):2960-2970.

PMID: 33121234 PMC: 8561284. DOI: 10.3324/haematol.2020.260158.

Calmodulin inhibitors improve erythropoiesis in Diamond-Blackfan anemia.

Taylor A, Macari E, Chan I, Blair M, Doulatov S, Vo L Sci Transl Med. 2020; 12(566).

PMID: 33087503 PMC: 7709865. DOI: 10.1126/scitranslmed.abb5831.

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