Hedgehog/GLI signaling in hematopoietic development and acute myeloid leukemia-From bench to bedside.
GLI proteins
acute myeloid leukemia
cancer stem cell
combination therapy
hedgehog (Hh) signaling
leukemic stem cell
smoothened inhibitor
tumor microenvironment
Journal
Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250
Informations de publication
Date de publication:
2022
2022
Historique:
received:
15
05
2022
accepted:
11
07
2022
entrez:
22
8
2022
pubmed:
23
8
2022
medline:
23
8
2022
Statut:
epublish
Résumé
While the underlying genetic alterations and biology of acute myeloid leukemia (AML), an aggressive hematologic malignancy characterized by clonal expansion of undifferentiated myeloid cells, have been gradually unraveled in the last decades, translation into clinical treatment approaches has only just begun. High relapse rates remain a major challenge in AML therapy and are to a large extent attributed to the persistence of treatment-resistant leukemic stem cells (LSCs). The Hedgehog (HH) signaling pathway is crucial for the development and progression of multiple cancer stem cell driven tumors, including AML, and has therefore gained interest as a therapeutic target. In this review, we give an overview of the major components of the HH signaling pathway, dissect HH functions in normal and malignant hematopoiesis, and specifically elaborate on the role of HH signaling in AML pathogenesis and resistance. Furthermore, we summarize preclinical and clinical HH inhibitor studies, leading to the approval of the HH pathway inhibitor glasdegib, in combination with low-dose cytarabine, for AML treatment.
Identifiants
pubmed: 35990601
doi: 10.3389/fcell.2022.944760
pii: 944760
pmc: PMC9388743
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
944760Informations de copyright
Copyright © 2022 Tesanovic, Krenn and Aberger.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Semin Cell Dev Biol. 2014 Sep;33:93-104
pubmed: 24852887
N Engl J Med. 2013 May 30;368(22):2059-74
pubmed: 23634996
Future Oncol. 2019 Nov;15(31):3531-3545
pubmed: 31516032
Leukemia. 2017 Apr;31(4):798-807
pubmed: 28111462
Cancer Sci. 2016 Oct;107(10):1422-1429
pubmed: 27461445
N Engl J Med. 1999 Sep 30;341(14):1051-62
pubmed: 10502596
Blood. 2014 Sep 25;124(13):2061-71
pubmed: 25049282
Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4254-9
pubmed: 19246386
Clin Cancer Res. 2017 May 15;23(10):2377-2381
pubmed: 28073840
Cancers (Basel). 2021 Sep 29;13(19):
pubmed: 34638372
Exp Hematol. 1990 Feb;18(2):114-8
pubmed: 2303103
Oncotarget. 2016 May 31;7(22):33004-15
pubmed: 27105509
Cancer Sci. 2017 Aug;108(8):1628-1633
pubmed: 28556364
Nat Genet. 1996 Sep;14(1):78-81
pubmed: 8782823
Cancers (Basel). 2021 Aug 23;13(16):
pubmed: 34439381
Cancer Cell. 2008 Sep 9;14(3):238-49
pubmed: 18772113
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Oncotarget. 2017 Apr 25;8(17):29187-29201
pubmed: 28418873
Cell. 2012 Oct 12;151(2):414-26
pubmed: 23063129
Leukemia. 2014 Sep;28(9):1774-83
pubmed: 24699305
Nat Med. 2014 Jul;20(7):732-40
pubmed: 24973920
Curr Top Dev Biol. 2022;149:203-261
pubmed: 35606057
Oncotarget. 2016 Feb 9;7(6):7134-48
pubmed: 26784250
Oncotarget. 2017 Jan 3;8(1):833-845
pubmed: 27903983
Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12561-6
pubmed: 15314219
J Cell Biol. 2010 Oct 18;191(2):415-28
pubmed: 20956384
Cell Stem Cell. 2009 Jun 5;4(6):548-58
pubmed: 19497283
Dev Cell. 2005 Mar;8(3):389-400
pubmed: 15737934
Development. 2001 Dec;128(24):5161-72
pubmed: 11748151
Int J Mol Sci. 2020 Jul 18;21(14):
pubmed: 32708452
Blood. 2017 Mar 23;129(12):1577-1585
pubmed: 28159741
Vitam Horm. 2012;88:25-54
pubmed: 22391298
Nature. 2004 Nov 18;432(7015):324-31
pubmed: 15549094
Vitam Horm. 2012;88:211-27
pubmed: 22391305
Cancer Cell. 2018 Sep 10;34(3):483-498.e5
pubmed: 30205048
Development. 2009 Aug;136(15):2613-21
pubmed: 19570846
Sci Transl Med. 2015 Jun 10;7(291):291ra96
pubmed: 26062848
Cell. 2008 Dec 12;135(6):1118-29
pubmed: 19062086
Am J Hematol. 2018 Nov;93(11):1301-1310
pubmed: 30074259
N Engl J Med. 2010 Dec 16;363(25):2424-33
pubmed: 21067377
Expert Rev Anticancer Ther. 2019 Aug;19(8):717-729
pubmed: 31422721
Blood. 2016 Sep 29;128(13):1671-8
pubmed: 27421961
J Biol Chem. 2002 Sep 20;277(38):35156-61
pubmed: 12138125
Cancer Biol Med. 2016 Jun;13(2):248-59
pubmed: 27458532
Nat Rev Mol Cell Biol. 2002 Nov;3(11):813-25
pubmed: 12415299
Nat Immunol. 2001 Feb;2(2):172-80
pubmed: 11175816
Ann Hematol. 2021 Dec;100(12):2933-2941
pubmed: 34333666
Nat Med. 2017 Oct 6;23(10):1124-1134
pubmed: 28985214
Nature. 1980 Oct 30;287(5785):795-801
pubmed: 6776413
Development. 2000 Apr;127(8):1593-605
pubmed: 10725236
Cancer Res. 2005 Nov 1;65(21):9643-50
pubmed: 16266983
J Clin Oncol. 1988 Apr;6(4):583-7
pubmed: 3282032
Development. 2002 Jan;129(2):361-72
pubmed: 11807029
Cancers (Basel). 2019 Apr 15;11(4):
pubmed: 30991683
Blood. 2010 Mar 25;115(12):2391-6
pubmed: 20107231
Clin Cancer Res. 2013 May 1;19(9):2289-93
pubmed: 23515405
Nat Med. 1997 Jul;3(7):730-7
pubmed: 9212098
Cells. 2020 Sep 17;9(9):
pubmed: 32957513
Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2548-53
pubmed: 24550281
Curr Opin Genet Dev. 2005 Feb;15(1):97-101
pubmed: 15661539
Blood Cancer J. 2012 Sep 07;2:e87
pubmed: 22961059
Nature. 1999 Feb 18;397(6720):617-21
pubmed: 10050855
Blood Res. 2020 Jul 31;55(S1):S1-S4
pubmed: 32719169
Nature. 2014 Jul 3;511(7507):90-3
pubmed: 24870236
Nat Med. 2007 Aug;13(8):944-51
pubmed: 17632527
Blood. 2004 Aug 15;104(4):1002-9
pubmed: 15105288
Mol Cell Biol. 2006 May;26(9):3365-77
pubmed: 16611981
Br J Haematol. 2019 May;185(3):595-598
pubmed: 30203489
Development. 1999 Sep;126(17):3915-24
pubmed: 10433919
Science. 1996 Jul 12;273(5272):242-5
pubmed: 8662508
Cell Signal. 2015 Feb;27(2):373-81
pubmed: 25435423
Annu Rev Cell Dev Biol. 2011;27:513-37
pubmed: 21801010
J Dev Biol. 2017 Nov 21;5(4):
pubmed: 29615569
FEBS J. 2021 Oct 6;:
pubmed: 34614300
Clin Cancer Res. 2018 May 15;24(10):2294-2303
pubmed: 29463550
J Biol Chem. 2009 Aug 21;284(34):22888-97
pubmed: 19556240
EMBO Mol Med. 2022 Apr 7;14(4):e14990
pubmed: 35253392
Nature. 2013 Feb 28;494(7438):484-8
pubmed: 23446420
Nat Med. 2018 Mar;24(3):271-281
pubmed: 29400712
Sci Signal. 2018 Sep 11;11(547):
pubmed: 30206138
Blood. 2017 Mar 23;129(12):1627-1635
pubmed: 28159738
Cell Stem Cell. 2009 Jun 5;4(6):559-67
pubmed: 19497284
Nat Med. 2013 Nov;19(11):1410-22
pubmed: 24202394
Nature. 2009 Apr 9;458(7239):776-9
pubmed: 19169242
Lancet Haematol. 2015 Aug;2(8):e339-46
pubmed: 26688487
Biomed Pharmacother. 2021 Jan;133:111054
pubmed: 33254022
Leukemia. 2011 Nov;25(11):1665-73
pubmed: 21660044
Clin Cancer Res. 2015 May 15;21(10):2388-98
pubmed: 25745035
Blood. 2016 Apr 21;127(16):2018-27
pubmed: 26834243
Cancer Res. 2017 Aug 15;77(16):4448-4459
pubmed: 28652248
Front Oncol. 2018 Oct 12;8:444
pubmed: 30370251
Nat Cell Biol. 2010 Feb;12(2):132-42
pubmed: 20081843
Int J Cancer. 2018 Mar 1;142(5):968-975
pubmed: 29055107
Endocrinology. 2004 Aug;145(8):3961-70
pubmed: 15132968
Cell Commun Signal. 2017 Jan 25;15(1):8
pubmed: 28122581
Nature. 2014 Feb 20;506(7488):328-33
pubmed: 24522528
Semin Cell Dev Biol. 2014 Sep;33:81-92
pubmed: 24862854
Leukemia. 2008 Jan;22(1):226-8
pubmed: 17928882
Cell. 1993 Dec 31;75(7):1417-30
pubmed: 7916661
Oncogene. 2018 Feb 8;37(6):787-797
pubmed: 29059168
Cell Physiol Biochem. 2016;38(4):1288-302
pubmed: 27008269
Genes Dev. 2010 Apr 1;24(7):670-82
pubmed: 20360384
Blood. 2016 May 19;127(20):2391-405
pubmed: 27069254
N Engl J Med. 2015 Sep 17;373(12):1136-52
pubmed: 26376137
Nature. 2008 Sep 18;455(7211):406-10
pubmed: 18754008
Cell Stem Cell. 2015 Oct 1;17(4):412-21
pubmed: 26387756
Cell Death Dis. 2021 Mar 3;12(3):231
pubmed: 33658491
Front Genet. 2019 Jun 12;10:556
pubmed: 31244888
Mech Dev. 1997 Mar;62(2):197-211
pubmed: 9152011
Blood. 2009 Apr 23;113(17):4074-7
pubmed: 18483393
Nat Rev Genet. 2010 May;11(5):331-44
pubmed: 20395968
Biochim Biophys Acta. 2010 Apr;1805(2):181-208
pubmed: 20085802
Acta Pharm Sin B. 2021 Mar;11(3):609-620
pubmed: 33777671
Leukemia. 2019 Feb;33(2):379-389
pubmed: 30555165
Exp Hematol. 2016 Dec;44(12):1181-1187.e2
pubmed: 27612547
Development. 2003 Dec;130(25):6233-43
pubmed: 14602680
Blood. 2007 Sep 15;110(6):1814-23
pubmed: 17536012
Genes Dev. 1999 Aug 15;13(16):2072-86
pubmed: 10465785
Blood. 2017 Jan 26;129(4):424-447
pubmed: 27895058
Oncogene. 2007 Feb 15;26(7):1046-55
pubmed: 16909105
Epigenetics. 2014 Aug;9(8):1108-19
pubmed: 24866170
Cancer Cell. 2012 Mar 20;21(3):374-87
pubmed: 22439934
J Clin Oncol. 2011 Feb 10;29(5):475-86
pubmed: 21220609
Blood. 1992 Jan 15;79(2):313-9
pubmed: 1730080
Trends Cell Biol. 2007 Sep;17(9):438-47
pubmed: 17845852
Oncotarget. 2017 Jul 1;8(40):67891-67903
pubmed: 28978082
J Natl Cancer Inst. 2010 Aug 4;102(15):1148-59
pubmed: 20660365
Blood. 2009 Jul 30;114(5):995-1004
pubmed: 19483124
N Engl J Med. 2005 Jan 20;352(3):254-66
pubmed: 15659725
Blood Cancer Discov. 2020 Aug 11;1(2):134-145
pubmed: 34661144
Lancet. 2013 Feb 9;381(9865):484-95
pubmed: 23399072
Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5895-900
pubmed: 17392427
Blood. 2005 Dec 1;106(12):3747-54
pubmed: 16109776
Oncotarget. 2011 Aug;2(8):638-45
pubmed: 21860067
Mol Cancer. 2016 Mar 18;15:24
pubmed: 26988232
Ann Hematol. 2021 May;100(5):1181-1194
pubmed: 33740113
Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12044-9
pubmed: 11027307
Blood. 2005 Aug 1;106(3):899-902
pubmed: 15831697
Expert Rev Anticancer Ther. 2003 Oct;3(5):695-710
pubmed: 14599092
Blood Cancer J. 2021 Feb 22;11(2):41
pubmed: 33619261
Mol Cancer Res. 2008 Dec;6(12):1928-36
pubmed: 19074837
Stem Cells Int. 2017;2017:2925869
pubmed: 28356914
Genes Dev. 2001 Dec 1;15(23):3059-87
pubmed: 11731473
Blood. 2017 Jun 29;129(26):3465-3475
pubmed: 28487292
Nature. 1996 Oct 3;383(6599):407-13
pubmed: 8837770
Dev Dyn. 2011 Apr;240(4):766-74
pubmed: 21337666
PLoS One. 2013 Jun 06;8(6):e65718
pubmed: 23762415
Cancer Sci. 2009 May;100(5):948-55
pubmed: 19245435
Nat Rev Cancer. 2020 Mar;20(3):158-173
pubmed: 31907378
PLoS Biol. 2011 Jun;9(6):e1001083
pubmed: 21695114
J Hematol Oncol. 2020 Jul 14;13(1):92
pubmed: 32664995
Ann Hematol. 2022 Aug;101(8):1689-1701
pubmed: 35488900
Cell. 2001 Jun 15;105(6):781-92
pubmed: 11440720
Development. 1997 Jan;124(1):113-23
pubmed: 9006072
J Immunol. 2013 Mar 15;190(6):2641-9
pubmed: 23408837
Crit Rev Eukaryot Gene Expr. 2010;20(2):129-39
pubmed: 21133842
Development. 2001 May;128(10):1717-30
pubmed: 11311154
J Hematol Oncol. 2015 Oct 20;8:114
pubmed: 26483188
Development. 2005 Oct;132(19):4407-17
pubmed: 16155214
Cells. 2019 Apr 25;8(4):
pubmed: 31027259
Cell. 2010 Jan 8;140(1):148-60
pubmed: 20074523
Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):14134-9
pubmed: 16968775