Bcor insufficiency promotes initiation and progression of myelodysplastic syndrome.

Blood
Shiro TaraAtsushi Iwama

Abstract

BCOR, encoding BCL-6 corepressor (BCOR), is X-linked and targeted by somatic mutations in various hematological malignancies including myelodysplastic syndrome (MDS). We previously reported that mice lacking Bcor exon 4 (Bcor ΔE4/y ) in the hematopoietic compartment developed NOTCH-dependent acute T-cell lymphoblastic leukemia (T-ALL). Here, we analyzed mice lacking Bcor exons 9 and 10 (Bcor ΔE9-10/y ), which express a carboxyl-terminal truncated BCOR that fails to interact with core effector components of polycomb repressive complex 1.1. Bcor ΔE9-10/y mice developed lethal T-ALL in a similar manner to Bcor ΔE4/y mice, whereas Bcor ΔE9-10/y hematopoietic cells showed a growth advantage in the myeloid compartment that was further enhanced by the concurrent deletion of Tet2 Tet2 Δ/Δ Bcor ΔE9-10/y mice developed lethal MDS with progressive anemia and leukocytopenia, inefficient hematopoiesis, and the morphological dysplasia of blood cells. Tet2 Δ/Δ Bcor ΔE9-10/y MDS cells reproduced MDS or evolved into lethal MDS/myeloproliferative neoplasms in secondary recipients. Transcriptional profiling revealed the derepression of myeloid regulator genes of the Cebp family and Hoxa cluster genes in Bcor ΔE9-10/y progenitor cells and the acti...Continue Reading

References

Sep 1, 2006·Molecular and Cellular Biology·Micah D GearhartVivian J Bardwell
Dec 22, 2007·Nature Reviews. Immunology·Ulf Klein, Riccardo Dalla-Favera
Nov 24, 2012·Nature Reviews. Cancer·Azra Raza, Naomi Galili
Nov 13, 2013·The Journal of Clinical Investigation·Daichi InoueToshio Kitamura
Nov 13, 2013·The Journal of Experimental Medicine·Tomoya MutoAtsushi Iwama
Jan 15, 2014·Genome Research·Shinji MaegawaJean-Pierre J Issa
Jan 1, 2015·Blood·R Coleman LindsleyBenjamin L Ebert
Jun 23, 2015·Nature Communications·Anand BalasubramaniAnjana Rao
Oct 16, 2015·Nature·Dan A LandauCatherine J Wu
Jan 17, 2016·Genes, Chromosomes & Cancer·Akito DobashiKengo Takeuchi
Mar 2, 2016·Haematologica·Friederike Pastore, Ross L Levine
Jul 28, 2016·Nature Reviews. Cancer·Laura Belver, Adolfo Ferrando
Aug 23, 2017·The Journal of Experimental Medicine·Tomoyuki TanakaAtsushi Iwama

❮ Previous
Next ❯

Citations

Dec 6, 2018·International Journal of Hematology·Shuhei Asada, Toshio Kitamura
Feb 2, 2019·International Journal of Hematology·Goro SashidaAtsushi Iwama
Jun 5, 2020·Acta Neuropathologica Communications·David J PisapiaJuan Miguel Mosquera
Jun 14, 2019·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Ju-Yoon YoonCarlos Parra-Herran
Oct 14, 2020·Cancer Science·Hiroyoshi Kunimoto, Hideaki Nakajima
Dec 31, 2020·International Journal of Molecular Sciences·Satoshi Kaito, Atsushi Iwama
Apr 4, 2021·Cancers·Yotaro Ochi, Seishi Ogawa
Apr 10, 2021·Science·Gary DixonDanwei Huangfu
May 5, 2021·Blood·Paolo SportolettiBrunangelo Falini
Dec 28, 2021·Leukemia & Lymphoma·Maciej GiefingReiner Siebert

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Cancer Epigenetics Chromatin Complexes (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin complexes and their role in cancer epigenetics.

Cardiovascular Disease & TET2

Cardiovascular diseases are the number one cause of deaths globally. Tet methylcytosine dioxygenase 2 (TET2)-mediated hematopoiesis has been implicated in accelerating heart failure. Here is the latest research on cardiovascular diseases and TET2.

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.

Cancer Epigenetics and Chromatin (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin and its role in cancer epigenetics please follow this feed to learn more.