Advanced search
Publication Cover
Leukemia & Lymphoma Volume 60, 2019 - Issue 7
Submit an article Journal homepage
203
Views
5
CrossRef citations to date
0
Altmetric
Original Article

Retinoic acid and 6-formylindolo(3,2-b)carbazole (FICZ) combination therapy reveals putative targets for enhancing response in non-APL AML

Rodica P. BunaciuDepartment of Biomedical Sciences, Cornell University, Ithaca, NY, USA;
,
Robert J. MacDonaldDepartment of Biomedical Sciences, Cornell University, Ithaca, NY, USA;
,
Holly A. JensenDepartment of Biomedical Sciences, Cornell University, Ithaca, NY, USA; ;Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY, USA;
,
Feng GaoDepartment of Biomedical Sciences, Cornell University, Ithaca, NY, USA; ;Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China;
,
Xin WangDepartment of Biomedical Sciences, City University of Hong Kong, Hong Kong, China;
,
Lynn JohnsonCornell Statistical Unit, Cornell University, Ithaca, NY, USA
,
Jeffrey D. VarnerRobert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY, USA;
&
Andrew YenDepartment of Biomedical Sciences, Cornell University, Ithaca, NY, USA; Correspondence[email protected]
 show all
Pages 1697-1708 | Received 25 Jun 2018, Accepted 29 Oct 2018, Published online: 20 Dec 2018
 
Sample our Medicine, Dentistry, Nursing & Allied Health journals, sign in here to start your FREE access for 14 days

Abstract

In non-acute promyelotic leukemia (APL)- non myelocytic leukemia (AML), identification of a signaling signature would predict potentially actionable targets to enhance differentiation effects of all-trans-retinoic acid (RA) and make combination differentiation therapy realizable. Components of such a signaling machine/signalsome found to drive RA-induced differentiation discerned in a FAB M2 cell line/model (HL-60) were further characterized and then compared against AML patient expression profiles. FICZ, known to enhance RA-induced differentiation, was used to experimentally augment signaling for analysis. FRET revealed novel signalsome protein associations: CD38 with pS376SLP76 and caveolin-1 with CD38 and AhR. The signaling molecules driving differentiation in HL-60 cluster in non-APL AML de novo samples, too. Pearson correlation coefficients for this molecular ensemble are nearer 1 in the FAB M2 subtype than in non-APL AML. SLP76 correlation to RXRα and p47phox were conserved in FAB M2 model and patient subtype but not in general non-APL AML. The signalsome ergo identifies potential actionable targets in AML.

Acknowledgments

This work was supported by grant R01 CA152870 from the National Institutes of Health (AY) and by the Center on the Physics of Cancer Metabolism through Award Number 1U54CA210184-01 from the National Cancer Institute.

Potential conflict of interest

Disclosure forms provided by the author are available with full text of this article at https://doi.org/10.1080/10428194.2018.1543880

Log in via your institution

Access through your institution

Log in to Taylor & Francis Online

Restore content access

Restore content access for purchases made as guest
Purchase options * Save for later

PDF download + Online access

  • 48 hours access to article PDF & online version
  • Article PDF can be downloaded
  • Article PDF can be printed
USD 65.00 Add to cart

Issue Purchase

  • 30 days online access to complete issue
  • Article PDFs can be downloaded
  • Article PDFs can be printed
USD 1,065.00 Add to cart

* Local tax will be added as applicable

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.