title: Microenvironmental remodeling as a parameter and prognostic factor of heterogeneous leukemogenesis in acute myelogenous leukemia.
abstract: Acute myelogenous leukemia (AML) is a heterogeneous disorder characterized by clonal proliferation of stem cell-like blasts in bone marrow (BM); however, their unique cellular interaction within the BM microenvironment and its functional significance remain unclear. Here, we assessed the BM microenvironment of AML patients and demonstrate that the leukemia stem cells induce a change in the transcriptional programming of the normal mesenchymal stromal cells (MSC). The modified leukemic niche alters the expressions of cross-talk molecules (i.e., CXCL12 and JAG1) in MSCs to provide a distinct cross-talk between normal and leukemia cells, selectively suppressing normal primitive hematopoietic cells while supporting leukemogenesis and chemoresistance. Of note, AML patients exhibited distinct heterogeneity in the alteration of mesenchymal stroma in BM. The distinct pattern of stromal changes in leukemic BM at initial diagnosis was associated with a heterogeneous posttreatment clinical course with respect to the maintenance of complete remission for 5 to 8 years and early or late relapse. Thus, remodeling of mesenchymal niche by leukemia cells is an intrinsic self-reinforcing process of leukemogenesis that can be a parameter for the heterogeneity in the clinical course of leukemia and hence serve as a potential prognostic factor.
authors: Catholic High-Performance Cell Therapy Center, The Catholic University of Korea, Seoul, Republic of Korea. Department of Medical Lifescience, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Jin-A
authors: JA
authors: Kim
authors: Catholic High-Performance Cell Therapy Center, The Catholic University of Korea, Seoul, Republic of Korea. Department of Medical Lifescience, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Jae-Seung
authors: JS
authors: Shim
authors: Catholic High-Performance Cell Therapy Center, The Catholic University of Korea, Seoul, Republic of Korea. Department of Medical Lifescience, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Ga-Young
authors: GY
authors: Lee
authors: Department of Preventive Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Hyeon Woo
authors: HW
authors: Yim
authors: Center for Cancer Evolution, Medical Research Center, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Tae-Min
authors: TM
authors: Kim
authors: Department of Laboratory Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Myungshin
authors: M
authors: Kim
authors: Department of Biological Science, Dong-A University, Busan, Republic of KoreaSouth Korea.
authors: Sun-Hee
authors: SH
authors: Leem
authors: Catholic Stem Cell Transplantation Center, Seoul St. Mary's Hospital, Seoul, Republic of Korea.
authors: Jong-Wook
authors: JW
authors: Lee
authors: Catholic Stem Cell Transplantation Center, Seoul St. Mary's Hospital, Seoul, Republic of Korea.
authors: Chang-Ki
authors: CK
authors: Min
authors: Catholic High-Performance Cell Therapy Center, The Catholic University of Korea, Seoul, Republic of Korea. Department of Medical Lifescience, The Catholic University of Korea, Seoul, Republic of Korea. iho@catholic.ac.kr.
authors: Il-Hoan
authors: IH
authors: Oh
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D054377:Chemokine CXCL12 / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D000072100:Jagged-1 Protein; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D011379:Prognosis; D000072099:Serrate-Jagged Proteins; D055153:Stem Cell Niche / Q000235:genetics; D059016:Tumor Microenvironment / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: C515255:CXCL12 protein, human; D002135:Calcium-Binding Proteins; D054377:Chemokine CXCL12; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D000072099:Serrate-Jagged Proteins