AML1 mutations induced MDS and MDS/AML in a mouse BMT model

Blood
Naoko Watanabe-OkochiToshio Kitamura

Abstract

Myelodysplastic syndrome (MDS) is a hematopoietic stem-cell disorder characterized by trilineage dysplasia and susceptibility to acute myelogenous leukemia (AML). Analysis of molecular basis of MDS has been hampered by the heterogeneity of the disease. Recently, mutations of the transcription factor AML1/RUNX1 have been identified in 15% to 40% of MDS-refractory anemia with excess of blasts (RAEB) and MDS/AML. We performed mouse bone marrow transplantation (BMT) using bone marrow cells transduced with the AML1 mutants. Most mice developed MDS and MDS/AML-like symptoms within 4 to 13 months after BMT. Interestingly, among integration sites identified, Evi1 seemed to collaborate with an AML1 mutant harboring a point mutation in the Runt homology domain (D171N) to induce MDS/AML with an identical phenotype characterized by marked hepatosplenomegaly, myeloid dysplasia, leukocytosis, and biphenotypic surface markers. Collaboration between AML1-D171N and Evi1 was confirmed by a BMT model where coexpression of AML1-D171N and Evi1 induced acute leukemia of the same phenotype with much shorter latencies. On the other hand, a C-terminal truncated AML1 mutant (S291fsX300) induced pancytopenia with erythroid dysplasia in transplanted mice,...Continue Reading

References

Aug 1, 1991·PCR Methods and Applications·C Arnold, I J Hodgson
Jul 18, 1995·Proceedings of the National Academy of Sciences of the United States of America·I RivièreR C Mulligan
Apr 16, 1996·Proceedings of the National Academy of Sciences of the United States of America·Q WangN A Speck
Jul 1, 1995·Current Opinion in Hematology·R D Legare, D G Gilliland
May 26, 1999·The New England Journal of Medicine·M L Heaney, D W Golde
Mar 4, 2000·Proceedings of the National Academy of Sciences of the United States of America·G M CuencoR Ren
Feb 13, 2001·British Journal of Haematology·S E LangabeerUNKNOWN MRC Adult Leukaemia Working Party
Mar 29, 2002·Genes, Chromosomes & Cancer·Stephen E LangabeerDavid C Linch
Jun 4, 2002·Current Opinion in Hematology·D Gary Gilliland, James D Griffin
Jun 19, 2002·Blood·Scott C KoganUNKNOWN Hematopathology subcommittee of the Mouse Models of Human Cancers Consortium
Oct 31, 2003·Experimental Hematology·Toshio KitamuraHidetoshi Kumagai
Nov 25, 2003·Hematology·Ghulam MuftiAloysius Y L Ho
Dec 19, 2003·Nucleic Acids Research·Keiko AkagiNeal G Copeland
Sep 3, 2004·The Journal of Clinical Investigation·Silvia BuonamiciGiuseppina Nucifora
Oct 13, 2004·Proceedings of the National Academy of Sciences of the United States of America·Timothy S FenskeTimothy A Graubert
Jul 19, 2005·The Journal of Clinical Investigation·Christina SchesslChristian Buske
Nov 12, 2005·British Journal of Haematology·Namiko YamashitaYoshiaki Ito
Nov 30, 2005·Gene·Giuseppina NuciforaVitalyi Senyuk

❮ Previous
Next ❯

Citations

Apr 8, 2009·International Journal of Hematology·Naoko Watanabe-OkochiToshio Kitamura
Jun 10, 2010·International Journal of Hematology·Susumu Goyama, Mineo Kurokawa
Dec 23, 2011·International Journal of Hematology·Noriko DokiToshio Kitamura
Oct 26, 2012·International Journal of Hematology·Yuki KagiyamaToshio Kitamura
Apr 25, 2013·International Journal of Hematology·Motoshi IchikawaMineo Kurokawa
Nov 24, 2012·Nature Reviews. Cancer·Azra Raza, Naomi Galili
Nov 6, 2009·The New England Journal of Medicine·Ayalew Tefferi, James W Vardiman
Dec 26, 2009·Human Molecular Genetics·Christopher R DowdyGary S Stein
May 27, 2009·Current Opinion in Hematology·Pearlie K Epling-Burnette, Alan F List
Nov 13, 2013·The Journal of Clinical Investigation·Daichi InoueToshio Kitamura
May 23, 2013·PloS One·Koutarou NishimuraToshio Kitamura
Apr 1, 2010·Epigenomics·Tamer E Fandy, Steven D Gore
Feb 4, 2014·Experimental Hematology·Tomoyuki UchidaToshio Kitamura
Sep 1, 2012·Annual Review of Pathology·R Coleman Lindsley, Benjamin L Ebert
Mar 6, 2009·Leukemia & Lymphoma·Peter Valent, Rotraud Wieser
Sep 1, 2011·Leukemia & Lymphoma·Brigitte SchlegelbergerMichael Heuser
Dec 17, 2014·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Toshio KitamuraJiro Kitaura
May 7, 2013·Experimental Hematology·Ting ZhouVivienne I Rebel
Jul 7, 2012·La Revue de médecine interne·T Cluzeau, P Fenaux
Sep 29, 2011·Seminars in Oncology·Alan H Shih, Ross L Levine
Apr 3, 2010·Hematology/oncology Clinics of North America·Rafael Bejar, Benjamin L Ebert
Apr 3, 2010·Hematology/oncology Clinics of North America·Sarah H Beachy, Peter D Aplan
Apr 1, 2009·Journal of Cellular Physiology·Yuka Harada, Hironori Harada
Mar 5, 2009·Journal of Cellular Physiology·Yukiko KomenoToshio Kitamura

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.