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Volume 8
Journal of Clinical & Experimental Pathology
ISSN : 2161-0681
Euro Pathology 2018 | Hematologic Oncology 2018
June 20-21, 2018
Page 44
Notes:
conference
series
.com
15
th
EUROPEAN PATHOLOGY CONGRESS
&
LEUKEMIA AND HEMATOLOGIC ONCOLOGY
June 20-21, 2018 | Paris, France
14
th
International Conference on
JOINT EVENT
Chandrika Gowda, J Clin Exp Pathol 2018, Volume 8
DOI: 10.4172/2161-0681-C1-044
Targeting casein kinase II (CK2) for treatment of high risk leukemia
A
cute lymphoblastic leukemia (ALL) is the most common cancer in children and accounts for highest death rate among
children aged 10-19 years. Current treatment for relapsed high risk ALL involves augmented chemotherapy, hematopoietic
stem cell transplant and radiation therapy which adds to the morbidity of already sick children. Recent genome-wide studies of
leukemic blasts have detected genetic lesions such as deletions or mutations in
IKZF1
. Alterations in
IKZF1
have proven to be
an indicator of inferior outcome in patients with high-risk ALL. Ikaros (
IKZF1
) functions as a master regulator of hematopoiesis
and a tumor suppressor in ALL. Ikaros binds to the upstream regulatory elements of its target genes and regulates their
transcription via chromatin remodeling. Casein kinase II (CK2) is a pro-oncogenic protein which is overexpressed in various
cancers including leukemia. Functional experiments showed that CK2-mediated phosphorylation of Ikaros, regulates Ikaros’
DNA binding affinity, subcellular localization, and protein stability. Dysregulation of several biological pathways in children
with high-risk B-ALL results fromCK2 overexpression and impaired Ikaros function. Targeted inhibition of CK2 restores Ikaros
tumor suppressor function in high-risk B-ALL even in cases with single allele Ikaros deletion. Treatment with the selective
CK2 inhibitor, CX4945 exhibits an anti-leukemic effect in primary xenograft models of high-risk B-ALL. Further studies use
precision medicine approaches (targeting specific pathways and/or functional defects) to develop novel drug combinations to
target these dysregulated pathways by inhibiting CK2 and restoring Ikaros tumor suppressor function as well as using a specific
inhibitor of the signaling pathway.
Biography
Chandrika Gowda is a Board Certified Pediatric Hematologist-Oncologist and Physician Scientist at Penn State Children’s Hospital and Penn State college of Medicine
in United States. After completing her training in 2013, she continued at PSU as an Assistant Professor. Her research focus for the past seven years has been in
pediatric leukemia, specifically to determine the mechanisms of tumor suppression by
IKZF1
gene and development of novel targeted therapies for treatment of high risk
pediatric leukemia and neuroblastoma. She has authored several publications and presented her work in various national and international scientific forums. She leads a
well-funded research program at PSU.
cgowda2@pennstatehealth.psu.eduChandrika Gowda
Pennsylvania State University, USA