The functional interplay of transcription factors and cell adhesion molecules in experimental myelodysplasia including hematopoietic stem progenitor compartment

Author(s):  
Suchismita Daw ◽  
Sujata Law
Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 311 ◽  
Author(s):  
Roland Windisch ◽  
Nina Pirschtat ◽  
Christian Kellner ◽  
Linping Chen-Wichmann ◽  
Jörn Lausen ◽  
...  

Numerous cell–cell and cell–matrix interactions within the bone marrow microenvironment enable the controlled lifelong self-renewal and progeny of hematopoietic stem and progenitor cells (HSPCs). On the cellular level, this highly mutual interaction is granted by cell adhesion molecules (CAMs) integrating differentiation, proliferation, and pro-survival signals from the surrounding microenvironment to the inner cell. However, cell–cell and cell–matrix interactions are also critically involved during malignant transformation of hematopoietic stem/progenitor cells. It has become increasingly apparent that leukemia-associated gene products, such as activated tyrosine kinases and fusion proteins resulting from chromosomal translocations, directly regulate the activation status of adhesion molecules, thereby directing the leukemic phenotype. These observations imply that interference with adhesion molecule function represents a promising treatment strategy to target pre-leukemic and leukemic lesions within the bone marrow niche. Focusing on myeloid leukemia, we provide a current overview of the mechanisms by which leukemogenic gene products hijack control of cellular adhesion to subsequently disturb normal hematopoiesis and promote leukemia development.


Blood ◽  
2010 ◽  
Vol 116 (9) ◽  
pp. 1422-1432 ◽  
Author(s):  
Yuka Nakamura ◽  
Fumio Arai ◽  
Hiroko Iwasaki ◽  
Kentaro Hosokawa ◽  
Isao Kobayashi ◽  
...  

Abstract The endosteal niche is critical for the maintenance of hematopoietic stem cells (HSCs). However, it consists of a heterogeneous population in terms of differentiation stage and function. In this study, we characterized endosteal cell populations and examined their ability to maintain HSCs. Bone marrow endosteal cells were subdivided into immature mesenchymal cell-enriched ALCAM−Sca-1+ cells, osteoblast-enriched ALCAM+Sca-1−, and ALCAM–Sca-1− cells. We found that all 3 fractions maintained long-term reconstitution (LTR) activity of HSCs in an in vitro culture. In particular, ALCAM+Sca-1− cells significantly enhanced the LTR activity of HSCs by the up-regulation of homing- and cell adhesion–related genes in HSCs. Microarray analysis showed that ALCAM−Sca-1+ fraction highly expressed cytokine-related genes, whereas the ALCAM+Sca-1− fraction expressed multiple cell adhesion molecules, such as cadherins, at a greater level than the other fractions, indicating that the interaction between HSCs and osteoblasts via cell adhesion molecules enhanced the LTR activity of HSCs. Furthermore, we found an osteoblastic markerlow/− subpopulation in ALCAM+Sca-1− fraction that expressed cytokines, such as Angpt1 and Thpo, and stem cell marker genes. Altogether, these data suggest that multiple subsets of osteoblasts and mesenchymal progenitor cells constitute the endosteal niche and regulate HSCs in adult bone marrow.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4126-4126
Author(s):  
Young-Ho Lee ◽  
Joong-Pyo Kim ◽  
Myung-Hwa Sung ◽  
Ri-Young Ko ◽  
Jin-Yeong Han

Abstract The hematologic values of neonatal peripheral blood show a characteristic series of changes during neonatal period. The hematopoietic stem cells in cord blood (CB) are more primitive and abundant than those in neonatal peripheral blood (NB). However, there have been no studies regarding the reasons for those differences. Thus, We investigated the kinetics of nucleated cells and CD34+ cells in CB and neonatal peripheral blood. We obtained the CB and NB samples from 14 normal full-term babies for this study, which were collected immediately after delivery as well as at 24 hours and 48 hours after delivery. We analysed the expressions of CD34, CD34/CXCR4, CD34/CD49d and CD34/CD44 as well as CD3, CD19 and CD16/56 on the isolated mononuclear cells by using FACSort. We also performed CFU-GM counts and apoptotic analysis with isolated mononuclear cells. The total white blood cell counts as well as absolute neutrophil counts of NB at delivery were higher than those of CB (p=0.04) and increased until 24 hours, when decreased until 48 hours after delivery. There were no differences of absolute lymphocyte counts, CD3+ cell and CD19+ cell counts among CB and NB at 0, 24 and 48 hours postnatally, however, the CD16/56+ cell counts were lower in CB than in NB and gradually decreased until 48 hours after delivery (p=0.011). The number of CFU-GM counts (p=0.02) and CD34+ cells (p=0.049) as well as CD34+CXCR4+ cells (p=0.002), CD34+CD49d+ (p=0.001) and CD34+CD44+ cells (p=0.001) in CB were more significantly higher than those of NB at delivery, when decreased gradually until 48 hours after delivery. The incidence of apoptosis were statistically not significant among CB and NB at 0, 24 and 48 hours postnatally. In conclusion, the higher leukocyte counts for several days after delivery were correlated with neutrophilic increment which may be influenced by stressful events during delivery. The more higher CFU-GM counts and CD34+ cell counts in CB than those in NB might be correlated with increased expression of cytokine receptors and cell adhesion molecules on the CD34+ cells in CB.


2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Yasushi Taniguchi

Hoxgenes encode homeodomain-containing transcription factors that determine cell and tissue identities in the embryo during development.Hoxgenes are also expressed in various adult tissues and cancer cells. InDrosophila, expression of cell adhesion molecules, cadherins and integrins, is regulated by Hox proteins operating in hierarchical molecular pathways and plays a crucial role in segment-specific organogenesis. A number of studies using mammalian cultured cells have revealed that cell adhesion molecules responsible for cell-cell and cell-extracellular matrix interactions are downstream targets of Hox proteins. However, whether Hox transcription factors regulate expression of cell adhesion molecules during vertebrate development is still not fully understood. In this review, the potential roles Hox proteins play in cell adhesion and migration during vertebrate body patterning are discussed.


2008 ◽  
Vol 6 ◽  
pp. CIN.S341 ◽  
Author(s):  
Anguraj Sadanandam ◽  
Sudipendra Nath Pal ◽  
Joe Ziskovsky ◽  
Prathibha Hegde ◽  
Rakesh K. Singh

In the post-genomic era, computational identification of cell adhesion molecules (CAMs) becomes important in defining new targets for diagnosis and treatment of various diseases including cancer. Lack of a comprehensive CAM-specific database restricts our ability to identify and characterize novel CAMs. Therefore, we developed a comprehensive mammalian cell adhesion molecule (MCAM) database. The current version is an interactive Web-based database, which provides the resources needed to search mouse, human and rat-specific CAMs and their sequence information and characteristics such as gene functions and virtual gene expression patterns in normal and tumor tissues as well as cell lines. Moreover, the MCAM database can be used for various bioinformatics and biological analyses including identifying CAMs involved in cell-cell interactions and homing of lymphocytes, hematopoietic stem cells and malignant cells to specific organs using data from high-throughput experiments. Furthermore, the database can also be used for training and testing existing transmembrane (TM) topology prediction methods specifically for CAM sequences. The database is freely available online at http://www.app1.unmc.edu/mcam .


Pharmacology ◽  
2007 ◽  
Vol 79 (3) ◽  
pp. 154-162 ◽  
Author(s):  
Ileana Manduteanu ◽  
Elena Dragomir ◽  
Manuela Voinea ◽  
Monica Capraru ◽  
Maya Simionescu

1999 ◽  
Vol 19 (5-6) ◽  
pp. 41 ◽  
Author(s):  
Francisco Sanchez-Madrid ◽  
Roberto González-Amaro

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 476-P
Author(s):  
YUSUKE TAKEDA ◽  
KEIICHIRO MATOBA ◽  
DAIJI KAWANAMI ◽  
YOSUKE NAGAI ◽  
TOMOYO AKAMINE ◽  
...  

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