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Dido gene expression alterations are implicated in the induction of hematological myeloid neoplasms
Agnes Fütterer, … , Jesús F. San Miguel, Carlos Martínez-A
Agnes Fütterer, … , Jesús F. San Miguel, Carlos Martínez-A
Published September 1, 2005
Citation Information: J Clin Invest. 2005;115(9):2351-2362. https://doi.org/10.1172/JCI24177.
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Research Article Hematology Article has an altmetric score of 4

Dido gene expression alterations are implicated in the induction of hematological myeloid neoplasms

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Abstract

The myelodysplastic/myeloproliferative diseases (MDS/MPDs) are a heterogeneous group of myeloid neoplasms that share characteristics with chronic myeloproliferative diseases and myelodysplastic syndromes. The broad spectrum of clinical manifestations makes MDS/MPDs extremely difficult to diagnose and treat, with a median survival time of 1–5 years. No single gene defect has been firmly associated with MDS/MPDs, and no animal models have been developed for these diseases. The association of deletions on chromosome 20q with myeloid malignancies suggests the presence of unidentified tumor suppressor genes in this region. Here we show that the recently identified death inducer–obliterator (Dido) gene gives rise to at least 3 polypeptides (Dido1, Dido2, and Dido3) through alternative splicing, and we map the human gene to the long arm of chromosome 20. We found that targeting of murine Dido caused a transplantable disease whose symptoms and signs suggested MDS/MPDs. Furthermore, 100% of human MDS/MPD patients analyzed showed Dido expression abnormalities, which we also found in other myeloid but not lymphoid neoplasms or in healthy donors. Our findings suggest that Dido might be one of the tumor suppressor genes at chromosome 20q and that the Dido-targeted mouse may be a suitable model for studying MDS/MPD diseases and testing new approaches to their diagnosis and treatment.

Authors

Agnes Fütterer, Miguel R. Campanero, Esther Leonardo, Luis M. Criado, Juana M. Flores, Jesús M. Hernández, Jesús F. San Miguel, Carlos Martínez-A

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Figure 7

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Severe reduction in hDido expression in bone marrow from MDS/MPD, MDS, a...
Severe reduction in hDido expression in bone marrow from MDS/MPD, MDS, and CMPD patients. (A) Relative hDido1, hDido2, and hDido3 expression levels were determined by real-time quantitative PCR. Ct increments relative to those of samples from a pool of healthy donors and actin (ΔΔCt) are shown for indicated patients. Note that a value of 3 in Ct increments indicates a 10-fold decrease in expression. (B) Northern blot analysis of hDido1, hDido2, and hDido3 expression in bone marrow samples of a healthy control donor (Ctl) and patients, indicated by numbers, diagnosed with various myeloid disorders. The blot was stained with methylene blue to control RNA loading. Positions of hDido transcripts and 28s and 18s RNA are indicated. Diagnosis of patients was as follows: chronic myelomonocytic leukemia (MDS/MPD), patients 15, 24, 25; refractory anemia (MDS), patients 2, 12, 17, 26, 30; polycythemia vera (CMPD), patients 7, 30; essential thrombocythemia (CMPD), patient 6; and refractory anemia with ringed sideroblasts (MDS), patient 23.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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