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Volume 8, Issue 5 (Suppl)
J Blood Disord Transfus, an open access journal
ISSN:2155-9864
Hematology 2017
November 08-09, 2017
November 08-09, 2017 | Las Vegas, USA
11
th
International Conference on
Hematology & Hematological Oncology
Autophagy in hematopoiesis and leukemogenesis
Jianrong Wang
Hematology Center of Cyrus Tang Medical Institute, China
A
utophagy, unique protective cytoplasmic machinery involving lysosomal degradation, is required for hematopoietic stem cell
multilineage differentiation that protects against leukemogenesis, but the underlying mechanism is unknown. We uncovered a
mechanistic link between autophagy and hematopoietic stem cell differentiation. Physiological autophagy activity was found to be
inversely correlated with Notch signaling during hematopoietic stem cell differentiation whilst pathologically low autophagy activity
was associated with upregulated Notch signaling in dysfunctional hematopoietic stem cells of leukemia patients. Furthermore, we
show that autophagy directly degrades intracellular Notch whereas conditional autophagy defects lead to elevated intracellular Notch
and its downstream targets as well as failed hematopoietic stem cell differentiation. Hematopoietic stem cell differentiation potential,
however, was restored in an autophagy defective systemwhen Notch signaling was pharmacologically or genetically abrogated. Finally,
we identified mitochondrial reactive oxygen species (ROS) as an upstream trigger for autophagy to physiologically downregulate
Notch signaling and drive hematopoietic stem cell differentiation. Hence, in the cause of development when mitochondrial
ROS are progressively produced, autophagy is triggered by the ROS to target Notch signaling to sustain hematopoietic stem cell
differentiation. Autophagy dysfunction is attributed to the differentiation blockades which are often the cause of hematological
malignancies. Therefore, our present findings provide a critical insight into the current mechanistic understanding of physiological
and pathological connections between autophagy and hematopoietic stem cell differentiation, thereby proposing a novel mechanism
by which autophagy maintains hematopoiesis and protects against leukemogenesis.
Biography
Jianrong Wang earned his PhD degree in The Shanghai Institute of Biochemistry, Chinese Academy of Sciences in July of 1997. In October of that year, he was appointed
as a Research Professor in a municipal institute in Shanghai China. After moving to US in January of 1999, he conducted research primarily at Cornell University. In March
of 2010, he was offered a professorial position at the Hematology Center of Cyrus Tang Medical Institute Soochow University. His laboratory focuses on the understanding
of the biology of autophagy in hematopoiesis and leukemogenesis, with an ultimate goal of preventing hematological oncogenic germination by protecting normal stem cells
from malignant transformation.
jrwang@suda.edu.cnJianrong Wang, J Blood Disord Transfus 2017, 8:5 (Suppl)
DOI: 10.4172/2155-9864-C1-028