TY - JOUR
T1 - Discovery of survival factor for primitive chronic myeloid leukemia cells using induced pluripotent stem cells
AU - Suknuntha, Kran
AU - Ishii, Yuki
AU - Tao, Lihong
AU - Hu, Kejin
AU - McIntosh, Brian E.
AU - Yang, David
AU - Swanson, Scott
AU - Stewart, Ron
AU - Wang, Jean Y.J.
AU - Thomson, James
AU - Slukvin, Igor
N1 - Funding Information:
We thank Dr. Toru Nakano for providing OP9 cells, Stem Cell Technologies for providing M2-10B4 cells, Mitchell Probasco for cell sorting, Oleg Moskvin for help with PCA analysis and Matt Raymond, Gene Ueneshi, Derek Theisen and Nicole Denison for editorial assistance. We also thank the Cell Processing and Manipulation Core in the Translational Cores, and Physicians and Nurses at UWCCC and CCHMC for obtaining and processing bone marrow samples and the Translational Research Trials Office for providing the regulatory and administrative support for this endeavor. This work was supported by funds from the National Institute of Health ( U01HL099773 , P01 GM081629 , P51 OD011106 , and P30 CA014520 ), and The Charlotte Geyer Foundation . K.S. is supported by funds from the Department of Pharmacology , Faculty of Science , Mahidol University, Bangkok, Thailand .
Publisher Copyright:
© 2015 The Authors.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - A definitive cure for chronic myeloid leukemia (CML) requires identifying novel therapeutic targets to eradicate leukemia stem cells (LSCs). However, the rarity of LSCs within the primitive hematopoietic cell compartment remains a major limiting factor for their study in humans. Here we show that primitive hematopoietic cells with typical LSC features, including adhesion defect, increased long-term survival and proliferation, and innate resistance to tyrosine kinase inhibitor (TKI) imatinib, can be generated de novo from reprogrammed primary CML cells. Using CML iPSC-derived primitive leukemia cells, we discovered olfactomedin 4 (OLFM4) as a novel factor that contributes to survival and growth of somatic lin-CD34+ cells from bone marrow of patients with CML in chronic phase, but not primitive hematopoietic cells from normal bone marrow. Overall, this study shows the feasibility and advantages of using reprogramming technology to develop strategies for targeting primitive leukemia cells.
AB - A definitive cure for chronic myeloid leukemia (CML) requires identifying novel therapeutic targets to eradicate leukemia stem cells (LSCs). However, the rarity of LSCs within the primitive hematopoietic cell compartment remains a major limiting factor for their study in humans. Here we show that primitive hematopoietic cells with typical LSC features, including adhesion defect, increased long-term survival and proliferation, and innate resistance to tyrosine kinase inhibitor (TKI) imatinib, can be generated de novo from reprogrammed primary CML cells. Using CML iPSC-derived primitive leukemia cells, we discovered olfactomedin 4 (OLFM4) as a novel factor that contributes to survival and growth of somatic lin-CD34+ cells from bone marrow of patients with CML in chronic phase, but not primitive hematopoietic cells from normal bone marrow. Overall, this study shows the feasibility and advantages of using reprogramming technology to develop strategies for targeting primitive leukemia cells.
UR - http://www.scopus.com/inward/record.url?scp=84946542062&partnerID=8YFLogxK
U2 - 10.1016/j.scr.2015.10.015
DO - 10.1016/j.scr.2015.10.015
M3 - Article
C2 - 26561938
AN - SCOPUS:84946542062
SN - 1873-5061
VL - 15
SP - 678
EP - 693
JO - Stem Cell Research
JF - Stem Cell Research
IS - 3
ER -