CEBPE activation in PML-RARA cells by arsenic

Z Hu, Y Saunthararajah - Blood, The Journal of the American …, 2012 - ashpublications.org
Blood, The Journal of the American Society of Hematology, 2012ashpublications.org
In a recent perspective, Ablain and de The challenged the classic model of acute
promyelocytic leukemia (APL), whereby differentiation-impairment in lineage-committed
progenitors causes self-renewal, and instead proposed that APL arises from deregulation of
stem cell self-renewal pathways in leukemia initiating cells, with the curative potential of
arsenic (As2O3) relating to abrogation of these pathways. 1 However, differentiation
syndrome occurs at a similar rate with As2O3 as with all-trans retinoic acid (ATRA), and …
In a recent perspective, Ablain and de The challenged the classic model of acute promyelocytic leukemia (APL), whereby differentiation-impairment in lineage-committed progenitors causes self-renewal, and instead proposed that APL arises from deregulation of stem cell self-renewal pathways in leukemia initiating cells, with the curative potential of arsenic (As2O3) relating to abrogation of these pathways. 1 However, differentiation syndrome occurs at a similar rate with As2O3 as with all-trans retinoic acid (ATRA), and furthermore, disseminated intravascular coagulation, the potentially fatal complication frequently triggered by cytotoxic treatment, is not typical. 2 Hence, clinical experience suggests that important actions of As2O3 include terminating APL proliferation by differentiation. To evaluate this further, the APL cell line NB4 was treated with low concentrations of As2O3 which do not induce early apoptosis3 (Figure 1A; supplemental Figure 1, available on the Blood Web site; see the Supplemental Materials link at the top
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