Maryam Samareh 1 Hematology Student Acute Promyelocytic Leukemia a distinct form of AML Accumulation of promyelocytes arrest of differentiation at the promyelocyte ID: 930166
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Slide1
Correlation between AHR and RA
Maryam
Samareh
1
Hematology Student
Slide2Acute
Promyelocytic
Leukemia
a distinct form of
AML
Accumulation of
promyelocytes
arrest of differentiation at the promyelocyte stage.
2
Slide3Treatment Of APL
3
Slide4All Trans Retinoid Acid
Retinoic Acid natural product of Retinol (
VitA
)
a key role in myeloid differentiation
Rate of complete remission 80–85
%
4
Slide5All Trans Retinoid Acid
the remission is not
durable
develop relapsed
resistant to retinoid
treatment
refractory
disease
combination therapy of RA &chemotherapy or Arsenic trioxid
5
AHR
Slide6Aryl Hydrocarbon Receptor
6
Slide77
Aryl Hydrocarbon Receptor
Slide88
AHR & RA
They compete
for the silencing
mediator
Teratogenic effects
such as cleft palate and
hydronephrosis
They can contribute to common developmental processesRAR and AhR
can also use the same
coactivators
Retinoids
are reported to be
AhR
ligands
crosstalk by
regulating the
same transcription factor,
Slide99
Oct4
Slide1010
AHR & Oct4
Slide1111
AHR & MAPK
Slide1212
Signalosome
Slide1313
Enhance differentiation
Rodica
P in 2013 FICZ modulates intracellular signaling pathways
and
enhances RA-induced
Rodica P in 2015 FICZ enhances RA-induced differentiation by AhR-dependent signaling effectsChristopher
N in 2014 VAF347 enhances
RA-induced granulocytic
differentiation
Slide1414
Refrences
Ibabao
CN, Bunaciu
RP, Schaefer DM, Yen A. The
AhR
agonist VAF347 augments retinoic acid-induced differentiation in leukemia cells. FEBS Open Bio. 2015;5:308-18
.Bunaciu RP, Yen A. Activation of the aryl hydrocarbon receptor AhR Promotes retinoic acid-induced differentiation of myeloblastic leukemia cells by restricting expression of the stem cell transcription factor Oct4. Cancer Res. 2011;71(6):2371-80.
Bunaciu
RP, Yen A. 6-Formylindolo (3,2-b)
carbazole
(FICZ) enhances retinoic acid (RA)-induced differentiation of HL-60
myeloblastic
leukemia cells.
Mol
Cancer. 2013;12(39):1476-4598.
Bunaciu
RP, Jensen HA, MacDonald RJ,
LaTocha
DH, Varner JD, Yen A. 6-Formylindolo(3,2-b)
Carbazole
(FICZ) Modulates the
Signalsome
Responsible for RA-Induced Differentiation of HL-60
Myeloblastic
Leukemia Cells.
PLoS
One. 2015;10(8
).
Zhang JW, Wang JY, Chen SJ, Chen Z. Mechanisms of all-trans retinoic acid-induced differentiation of acute
promyelocytic
leukemia cells. J
Biosci
. 2000;25(3):275-84.
Slide15115
Thank you for your attention