NDLI: The TPO/c-MPL pathway in the bone marrow may protect leukemia cells from chemotherapy in AML Patients.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Dong-Feng, Zeng Ting, Liu Yong, Zhang Cheng, Chang Xi, Zhang Pei-Yan, Kong
Description	Author Affiliation: Dong-Feng Z ( Department of Hematology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China.)
Abstract	Accumulating evidence indicates that the interaction of human LSCs (leukemic stem cells) with the hematopoietic microenvironment, mediated by the thrombopoietin (TPO)/c-MPL pathway, may be an underlying mechanism for resistance to cell cycle-dependent cytotoxic chemotherapy. However, the role of TPO/c-MPL signaling in AML (acute myelogenous leukemia) chemotherapy resistance hasn't been fully understood. The c-MPL and TPO levels in different AML samples were measured by flow cytometry and ELISA. We also assessed the TPO levels in the osteoblasts derived from bone mesenchymal stem cells (BMSCs). The survival rate of an AML cell line that had been co-cultured with different BMSC-derived osteoblasts was measured to determine the IC50 of an AML chemotherapy drug daunorubicin (DNR). The levels of TPO/c-MPL in the initial and relapse AML patients were significantly higher than that in the control (P < 0.05). The osteoblasts derived from AML patients' BMSCs secreted more TPO than the osteoblasts derived from normal control BMSCs (P < 0.05). A strong positive correlation between the TPO level and c-MPL expression was found in the bone marrow mononuclear cells of the relapse AML patients. More importantly, the IC50 of DNR in the HEL + AML-derived osteoblasts was the highest among all co-culture systems. High level of TPO/c-MPL signaling may protect LSCs from chemotherapy in AML. The effects of inhibition of the TPO/c-MPL pathway on enhancing the chemotherapy sensitivity of AML cells, and on their downstream effector molecules that direct the interactions between patient-derived blasts and leukemia repopulating cells need to be further studied.
File Format	HTM / HTML
ISSN	12194956
Issue Number	2
Volume Number	20
e-ISSN	15322807
Journal	Pathology & Oncology Research
Language	English
Publisher	Springer
Publisher Date	2014-04-01
Publisher Place	Netherlands
Access Restriction	Subscribed
Subject Keyword	Discipline Oncology Autoantigens Metabolism Bone Marrow Iodide Peroxidase Iron-binding Proteins Leukemia, Myeloid, Acute Mortality Receptors, Thrombopoietin Adolescent Adult Aged Case-control Studies Cell Cycle Physiology Cell Line Child Coculture Techniques Female Humans Male Middle Aged Osteoblasts Signal Transduction Stem Cells Survival Rate Young Adult Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Cancer Research Pathology and Forensic Medicine Oncology

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