Skip to content
2000
Volume 21, Issue 7
  • ISSN: 1573-3947
  • E-ISSN: 1875-6301

Abstract

Acute Myeloid Leukemia (AML), a malignant hematologic neoplasm marked by abnormal proliferation and infiltration of myeloid precursor cells into the bone marrow, exhibits the highest fatality rate. Homoharringtonine continues to demonstrate efficacy and dependability in the clinical management of AML. We have, herein, summarized a series of problems associated with HHT in the treatment of AML, including the mechanism of action of HHT combined with other drugs, drug resistance mechanisms, and action targets. With the emergence of drug resistance and disease recurrence, combination therapies have become a more effective clinical drug choice. Based on previous studies, we propose that β-catenin and GSK-3β may play a decisive role in p-eIf4E-mediated multidrug resistance. It is necessary to investigate whether HHT can bind to MCL-1 and downregulate its expression to overcome venetoclax’s resistance. Currently, there is an ongoing effort to conduct further mechanistic investigations into the combined use of HHT and other pharmaceuticals, aimed at enhancing therapeutic outcomes and addressing drug resistance in patients diagnosed with refractory AML.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cctr/10.2174/0115733947317749240918113844
2024-09-25
2025-12-05

  • From This Site

    /content/journals/cctr/10.2174/0115733947317749240918113844
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. PollardJ.A. AlonzoT.A. BrownP.A. GerbingR.B. FoxE. ChoiJ.K. FisherB.T. HirschB.A. KahwashS. LevineJ.E. LokenM.R. RaimondiS.C. TarlockK. WoodA.C. SungL. KolbA.E. GamisA.S. MeshinchiS. AplencR. Sorafenib in combination with standard chemotherapy for children with high allelic ratio FLT3/ITD+ AML improves event-free survival and reduces relapse risk: A report from the children’s oncology group protocol AAML1031.Blood2019134Suppl. 129210.1182/blood‑2019‑129557
     [Google Scholar]
  2. KalekaG. SchillerG. Immunotherapy for Acute Myeloid Leukemia: Allogeneic hematopoietic cell transplantation is here to stay.Leuk. Res.202211210673210.1016/j.leukres.2021.10673234864447
     [Google Scholar]
  3. OhtakeS. MiyawakiS. FujitaH. KiyoiH. ShinagawaK. UsuiN. OkumuraH. MiyamuraK. NakasekoC. MiyazakiY. FujiedaA. NagaiT. YamaneT. TaniwakiM. TakahashiM. YagasakiF. KimuraY. AsouN. SakamakiH. HandaH. HondaS. OhnishiK. NaoeT. OhnoR. Randomized study of induction therapy comparing standard-dose idarubicin with high-dose daunorubicin in adult patients with previously untreated acute myeloid leukemia: the JALSG AML201 Study.Blood201111782358236510.1182/blood‑2010‑03‑27324320693429
     [Google Scholar]
  4. SmithC.R.Jr PowellR.G. MikolajczakK.L. The genus Cephalotaxus: source of homoharringtonine and related anticancer alkaloids.Cancer Treat. Rep.197660811571170791485
     [Google Scholar]
  5. AllanE.K. HolyoakeT.L. CraigA.R. JørgensenH.G. Omacetaxine may have a role in chronic myeloid leukaemia eradication through downregulation of Mcl-1 and induction of apoptosis in stem/progenitor cells.Leukemia201125698599410.1038/leu.2011.5521468038
     [Google Scholar]
  6. ChenC. XuW. YangJ. Low-dose homoharringtonine and cytarabine in combination with granulocyte colony-stimulating factor for elderly patients with de novo acute myeloid leukemia.Leuk. Lymphoma201556114114610.3109/10428194.2014.91077424724783
     [Google Scholar]
  7. ZhuH.H. JiangH. JiangQ. JiaJ.S. QinY.Z. HuangX.J. Homoharringtonine, aclarubicin and cytarabine (HAA) regimen as the first course of induction therapy is highly effective for acute myeloid leukemia with t (8;21).Leuk. Res.201644404410.1016/j.leukres.2016.02.01226994850
     [Google Scholar]
  8. WarrellR.P.Jr CoonleyC.J. GeeT.S. Homoharringtonine: An effective new drug for remission induction in refractory nonlymphoblastic leukemia.J. Clin. Oncol.19853561762110.1200/JCO.1985.3.5.6173889229
     [Google Scholar]
  9. JinJ. WangJ.X. ChenF.F. WuD.P. HuJ. ZhouJ.F. HuJ.D. WangJ.M. LiJ.Y. HuangX.J. MaJ. JiC.Y. XuX.P. YuK. RenH.Y. ZhouY.H. TongY. LouY.J. NiW.M. TongH.Y. WangH.F. MiY.C. DuX. ChenB.A. ShenY. ChenZ. ChenS.J. Homoharringtonine-based induction regimens for patients with de novo acute myeloid leukaemia: A multicentre, open-label, randomised, controlled phase 3 trial.Lancet Oncol.201314759960810.1016/S1470‑2045(13)70152‑923664707
     [Google Scholar]
  10. MiR. ZhaoJ. ChenL. WeiX. LiuJ. WeiX. Efficacy and safety of homoharringtonine for the treatment of acute myeloid leukemia: A meta-analysis.Clin. Lymphoma Myeloma Leuk.20212110e752e76710.1016/j.clml.2021.06.00234301487
     [Google Scholar]
  11. LeungG.M.K. ZhangC.X. ToA.W.L. Combination of omacetaxine mepesuccinate (homoharringtonine) and sorafenib as an effective regimen for Acute Myeloid Leukemia (AML) carrying FLT3-ITD.Blood20171303849
     [Google Scholar]
  12. TangR. FaussatA.M. MajdakP. MarzacC. DubrulleS. MarjanovicZ. LegrandO. MarieJ.P. Semisynthetic homoharringtonine induces apoptosis via inhibition of protein synthesis and triggers rapid myeloid cell leukemia-1 down-regulation in myeloid leukemia cells.Mol. Cancer Ther.20065372373110.1158/1535‑7163.MCT‑05‑016416546987
     [Google Scholar]
  13. WuZ. ZhuangH. YuQ. ZhangX. JiangX. LuX. XuY. YangL. WuB. MaA. ZhangL. XiaoX. LiangY. GaoR. ShenJ. XuR. Homoharringtonine combined with the heat shock protein 90 inhibitor IPI504 in the treatment of FLT3-ITD acute myeloid leukemia.Transl. Oncol.201912680180910.1016/j.tranon.2019.02.01630953928
     [Google Scholar]
  14. LiX. YinX. WangH. HuangJ. YuM. MaZ. LiC. ZhouY. YanX. HuangS. JinJ. Correction: The combination effect of homoharringtonine and ibrutinib on FLT3-ITD mutant acute myeloid leukemia.Oncotarget201910616641664210.18632/oncotarget.2731031762943
     [Google Scholar]
  15. LamS.S.Y. HoE.S.K. HeB.L. WongW.W. CherC.Y. NgN.K.L. ManC.H. GillH. CheungA.M.S. IpH.W. SoC.C. TamburiniJ. SoC.W.E. HoD.N. AuC.H. ChanT.L. MaE.S.K. LiangR. KwongY.L. LeungA.Y.H. Homoharringtonine (omacetaxine mepesuccinate) as an adjunct for FLT3 - ITD acute myeloid leukemia.Sci. Transl. Med.20168359359ra12910.1126/scitranslmed.aaf373527708062
     [Google Scholar]
  16. ZhangT. ShenS. ZhuZ. LuS. YinX. ZhengJ. JinJ. Homoharringtonine binds to and increases myosin-9 in myeloid leukaemia.Br. J. Pharmacol.2016173121222110.1111/bph.1335926448459
     [Google Scholar]
  17. ChenX.J. ZhangW.N. ChenB. XiW.D. LuY. HuangJ.Y. WangY.Y. LongJ. WuS.F. ZhangY.X. WangS. LiS.X. YinT. LuM. XiX.D. LiJ.M. WangK.K. ChenZ. ChenS.J. Homoharringtonine deregulates MYC transcriptional expression by directly binding NF-κB repressing factor.Proc. Natl. Acad. Sci. USA201911662220222510.1073/pnas.181853911630659143
     [Google Scholar]
  18. TanM. ZhangQ. YuanX. ChenY. WuY. Correction to: Synergistic killing effects of homoharringtonine and arsenic trioxide on acute myeloid leukemia stem cells and the underlying mechanisms.J. Exp. Clin. Cancer Res.201938140710.1186/s13046‑019‑1377‑731526386
     [Google Scholar]
  19. ZhangJ. GengH. LiuL. ZhangH. Synergistic cytotoxicity of homoharringtonine and etoposide in acute myeloid leukemia cells involves disrupted antioxidant defense.Cancer Manag. Res.2019111023103210.2147/CMAR.S18759730774430
     [Google Scholar]
  20. LiC. DongL. SuR. BiY. QingY. DengX. ZhouY. HuC. YuM. HuangH. JiangX. LiX. HeX. ZouD. ShenC. HanL. SunM. SkibbeJ. FerchenK. QinX. WengH. HuangH. SongC. ChenJ. JinJ. Homoharringtonine exhibits potent anti-tumor effect and modulates DNA epigenome in acute myeloid leukemia by targeting SP1/TET1/5hmC.Haematologica2020105114816010.3324/haematol.2018.20883530975912
     [Google Scholar]
  21. KantarjianH.M. TalpazM. SantiniV. MurgoA. ChesonB. O’BrienS.M. Homoharringtonine.Cancer20019261591160510.1002/1097‑0142(20010915)92:6<1591::AID‑CNCR1485>3.0.CO;2‑U11745238
     [Google Scholar]
  22. SylvesterR.K. LobellM. OgdenW. StewartJ.A. Homoharringtonine-induced hyperglycemia.J. Clin. Oncol.19897339239510.1200/JCO.1989.7.3.3922645387
     [Google Scholar]
  23. SouersA.J. LeversonJ.D. BoghaertE.R. AcklerS.L. CatronN.D. ChenJ. DaytonB.D. DingH. EnschedeS.H. FairbrotherW.J. HuangD.C.S. HymowitzS.G. JinS. KhawS.L. KovarP.J. LamL.T. LeeJ. MaeckerH.L. MarshK.C. MasonK.D. MittenM.J. NimmerP.M. OleksijewA. ParkC.H. ParkC.M. PhillipsD.C. RobertsA.W. SampathD. SeymourJ.F. SmithM.L. SullivanG.M. TahirS.K. TseC. WendtM.D. XiaoY. XueJ.C. ZhangH. HumerickhouseR.A. RosenbergS.H. ElmoreS.W. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets.Nat. Med.201319220220810.1038/nm.304823291630
     [Google Scholar]
  24. ShiY. YeJ. YangY. ZhaoY. ShenH. YeX. XieW. The basic research of the combinatorial therapy of ABT-199 and homoharringtonine on acute myeloid leukemia.Front. Oncol.20211169249710.3389/fonc.2021.69249734336680
     [Google Scholar]
  25. YinZ. To enhance the anti-AML effect of homoharringtonine combined with venetoclax and explore its mechanism postgraduate, Southern Medical University, Guangzhou.2021Available from: https://link.cnki.net/doi/10.27003/d.cnki.gojyu.2021.000874doi:10.27003/d.cnki.gojyu.2021.000874
  26. YuanF.F. Synergistic efficacy of homoharringtonine and venetoclax on acute myeloid leukemia cells and the underlying mechanisms.Doctorate, Zhengzhou University, Zhengzhou202210.21037/atm‑22‑1459
     [Google Scholar]
  27. MillC.P. FiskusW. DiNardoC.D. BirdwellC. LaraB.H. KhouryJ.D. BhallaK.N. Preclinical efficacy of a novel omacetaxine-based therapy for aml expressing somatic or germline mutant RUNX1.Blood20201361Suppl. 1151610.1182/blood‑2020‑14174232430499
     [Google Scholar]
  28. MillC.P. FiskusW. DiNardoC.D. QianY. RainaK. RajapaksheK. PereraD. CoarfaC. KadiaT.M. KhouryJ.D. SaenzD.T. SaenzD.N. IllendulaA. TakahashiK. KornblauS.M. GreenM.R. FutrealA.P. BushwellerJ.H. CrewsC.M. BhallaK.N. RUNX1-targeted therapy for AML expressing somatic or germline mutation in RUNX1.Blood20191341597310.1182/blood.201889398231023702
     [Google Scholar]
  29. SchnittgerS. DickerF. KernW. WendlandN. SundermannJ. AlpermannT. HaferlachC. HaferlachT. RUNX1 mutations are frequent in de novo AML with noncomplex karyotype and confer an unfavorable prognosis.Blood201111782348235710.1182/blood‑2009‑11‑25597621148331
     [Google Scholar]
  30. MillC.P. FiskusW. DiNardoC.D. BirdwellC. DavisJ.A. KadiaT.M. TakahashiK. ShortN. DaverN. OhanianM. BorthakurG. KornblauS.M. GreenM.R. QiY. SuX. KhouryJ.D. BhallaK.N. Effective therapy for AML with RUNX1 mutation by cotreatment with inhibitors of protein translation and BCL2.Blood2022139690792110.1182/blood.202101315634601571
     [Google Scholar]
  31. YuG. XuN. HuangF. FanZ. LiuH. ShiP. ZhouH. WangZ. ZhangY. LiuQ. Combination of homoharringtonine with venetoclax and azacitidine excerts better treatment response in relapsed /refractory acute myeloid leukemia.Blood20201361Suppl. 1262710.1182/blood‑2020‑138676
     [Google Scholar]
  32. JinH. ZhangY. YuS. DuX. XuN. ShaoR. LinD. ChenY. XiaoJ. SunZ. DengL. LiangX. ZhangH. GuoZ. DaiM. ShiP. HuangF. FanZ. YinZ. XuanL. LinR. JiangX. YuG. LiuQ. Venetoclax combined with azacitidine and homoharringtonine in relapsed/refractory AML: A multicenter, phase 2 trial.J. Hematol. Oncol.20231614210.1186/s13045‑023‑01437‑137120593
     [Google Scholar]
  33. SongB.Q. KongX. PuY. LiuY. ZhangJ. WuD.P. QiuH.Y. Outcomes of venetoclax combined with homoharringtonine and cytarabine in fit adults patients with de novo adverse‐risk acute myeloid leukaemia: A single‐centre retrospective analysis.eJHaem2023441208121110.1002/jha2.79238024627
     [Google Scholar]
  34. FangD.D. ZhuH. TangQ. WangG. MinP. WangQ. LiN. YangD. ZhaiY. FLT3 inhibition by olverembatinib (HQP1351) downregulates MCL-1 and synergizes with BCL-2 inhibitor lisaftoclax (APG-2575) in preclinical models of FLT3-ITD mutant acute myeloid leukemia.Transl. Oncol.202215110124410.1016/j.tranon.2021.10124434710737
     [Google Scholar]
  35. WeiW. HuangS. LingQ. MaoS. QianY. YeW. LiF. PanJ. LinX. HuangJ. HuangX. ZhaiY. SunJ. JinJ. Homoharringtonine is synergistically lethal with BCL-2 inhibitor APG-2575 in acute myeloid leukemia.J. Transl. Med.202220129910.1186/s12967‑022‑03497‑235794605
     [Google Scholar]
  36. CaiJ. HuangH. HuX. LangW. FuW. XuL. QiuZ. ZhongH. ChenF. Homoharringtonine synergized with gilteritinib results in the downregulation of myeloid cell leukemia-1 by upregulating UBE2L6 in FLT3-ITD-Mutant acute myeloid (leukemia) cell lines.J. Oncol.2021202111110.1155/2021/376642834594375
     [Google Scholar]
  37. ZhangC. LamS.S.Y. LeungG.M.K. TsuiS.P. YangN. NgN.K.L. IpH.W. AuC.H. ChanT.L. MaE.S.K. YipS.F. LeeH.K.K. LauJ.S.M. LukT.H. LiW. KwongY.L. LeungA.Y.H. Sorafenib and omacetaxine mepesuccinate as a safe and effective treatment for acute myeloid leukemia carrying internal tandem duplication of Fms‐like tyrosine kinase 3.Cancer2020126234435310.1002/cncr.3253431580501
     [Google Scholar]
  38. QiuY. LiY. ChaiM. HuaH. WangR. WaxmanS. JingY. The GSK3β/Mcl-1 axis is regulated by both FLT3-ITD and Axl and determines the apoptosis induction abilities of FLT3-ITD inhibitors.Cell Death Discov.2023914410.1038/s41420‑023‑01317‑036739272
     [Google Scholar]
  39. BritoA.B.C. LourençoG.J. OliveiraG.B. De SouzaC.A. VassalloJ. LimaC.S.P. Associations of VEGF and VEGFR2 polymorphisms with increased risk and aggressiveness of multiple myeloma.Ann. Hematol.20149381363136910.1007/s00277‑014‑2062‑824687381
     [Google Scholar]
  40. ShiY. XuD. XuY. ShenH. ZhangY. YeX. JinJ. CuiD. XieW. Synergistic lethality effects of apatinib and homoharringtonine in acute myeloid leukemia.J. Oncol.2022202211310.1155/2022/900580436081666
     [Google Scholar]
  41. ZarrinkarP.P. GunawardaneR.N. CramerM.D. GardnerM.F. BrighamD. BelliB. KaramanM.W. PratzK.W. PallaresG. ChaoQ. SprankleK.G. PatelH.K. LevisM. ArmstrongR.C. JamesJ. BhagwatS.S. AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood2009114142984299210.1182/blood‑2009‑05‑22203419654408
     [Google Scholar]
  42. WeisT.M. MariniB.L. BixbyD.L. PerissinottiA.J. Clinical considerations for the use of FLT3 inhibitors in acute myeloid leukemia.Crit. Rev. Oncol. Hematol.201914112513810.1016/j.critrevonc.2019.06.01131279288
     [Google Scholar]
  43. WangF. HuangJ. GuoT. ZhengY. ZhangL. ZhangD. WangF. NarenD. CuiY. LiuX. QuY. LuoH. YangY. WeiH. GuoY. Homoharringtonine synergizes with quizartinib in FLT3-ITD acute myeloid leukemia by targeting FLT3-AKT-c-Myc pathway.Biochem. Pharmacol.202118811453810.1016/j.bcp.2021.11453833831397
     [Google Scholar]
  44. XuG. MaoL. LiuH. YangM. JinJ. QianW. Sorafenib in combination with low-dose-homoharringtonine as a salvage therapy in primary refractory FLT3-ITD-positive AML: A case report and review of literature.Int. J. Clin. Exp. Med.2015811198911989426884901
     [Google Scholar]
  45. JohnsonE. McTigueM. GallegoR.A. JohnsonT.W. TimofeevskiS. MaestreM. FisherT.S. KaniaR. SawasdikosolS. BurakoffS. CroninC.N. Multiple conformational states of the HPK1 kinase domain in complex with sunitinib reveal the structural changes accompanying HPK1 trans-regulation.J. Biol. Chem.2019294239029903610.1074/jbc.AC119.00746631018963
     [Google Scholar]
  46. GeJ. NormantE. PorterJ.R. AliJ.A. DembskiM.S. GaoY. GeorgesA.T. GrenierL. PakR.H. PattersonJ. SydorJ.R. TibbittsT.T. TongJ.K. AdamsJ. PalombellaV.J. Design, synthesis, and biological evaluation of hydroquinone derivatives of 17-amino-17-demethoxygeldanamycin as potent, water-soluble inhibitors of Hsp90.J. Med. Chem.200649154606461510.1021/jm060311616854066
     [Google Scholar]
  47. ElagibK.E. GoldfarbA.N. Oncogenic pathways of AML1-ETO in acute myeloid leukemia: Multifaceted manipulation of marrow maturation.Cancer Lett.2007251217918610.1016/j.canlet.2006.10.01017125917
     [Google Scholar]
  48. LeiY. ChenX. DaiY. DaiB. WangJ. LiM. LiuP. LiuH. WangK. JiangL. ChenB. Combination of eriocalyxin B and homoharringtonine exerts synergistic anti-tumor effects against t(8;21) AML.Acta Pharmacol. Sin.202445363364510.1038/s41401‑023‑01196‑238017299
     [Google Scholar]
  49. WangJ. LüS. YangJ. SongX. ChenL. HuangC. HouJ. ZhangW. A homoharringtonine-based induction regimen for the treatment of elderly patients with acute myeloid leukemia: A single center experience from China.J. Hematol. Oncol.2009213210.1186/1756‑8722‑2‑3219642997
     [Google Scholar]
  50. GregoryM.A. NemkovT. ParkH.J. ZaberezhnyyV. GehrkeS. AdaneB. JordanC.T. HansenK.C. D’AlessandroA. DeGregoriJ. Targeting glutamine metabolism and redox state for leukemia therapy.Clin. Cancer Res.201925134079409010.1158/1078‑0432.CCR‑18‑322330940653
     [Google Scholar]
  51. RawlingsD.J. SaffranD.C. TsukadaS. LargaespadaD.A. GrimaldiJ.C. CohenL. MohrR.N. BazanJ.F. HowardM. CopelandN.G. JenkinsN.A. WitteO.N. Mutation of unique region of Bruton’s tyrosine kinase in immunodeficient XID mice.Science1993261511935836110.1126/science.83329018332901
     [Google Scholar]
  52. HuangS. PanJ. JinJ. LiC. LiX. HuangJ. HuangX. YanX. LiF. YuM. HuC. JinJ. XuY. LingQ. YeW. WangY. JinJ. Abivertinib, a novel BTK inhibitor: Anti-Leukemia effects and synergistic efficacy with homoharringtonine in acute myeloid leukemia.Cancer Lett.201946113214310.1016/j.canlet.2019.07.00831310800
     [Google Scholar]
  53. HacklH. AstaninaK. WieserR. Molecular and genetic alterations associated with therapy resistance and relapse of acute myeloid leukemia.J. Hematol. Oncol.20171015110.1186/s13045‑017‑0416‑028219393
     [Google Scholar]
  54. ZhangW. LuY. ZhenT. ChenX. ZhangM. LiuP. WengX. ChenB. WangY. Homoharringtonine synergy with oridonin in treatment of t(8; 21) acute myeloid leukemia.Front. Med.201913338839710.1007/s11684‑018‑0624‑130206768
     [Google Scholar]
  55. ChenP. ZhanW. WangB. YouP. JinQ. HouD. WangX. YouR. ZouH. ChenY. HuangH. Homoharringtonine potentiates the antileukemic activity of arsenic trioxide against acute myeloid leukemia cells.Exp. Cell Res.2019376211412310.1016/j.yexcr.2019.02.00830763586
     [Google Scholar]
  56. WangL. YouL.S. NiW.M. MaQ.L. TongY. MaoL.P. QianJ.J. JinJ. β-Catenin and AKT are promising targets for combination therapy in acute myeloid leukemia.Leuk. Res.201337101329134010.1016/j.leukres.2013.06.02323867056
     [Google Scholar]
  57. LiF. LingQ. HuC. WangH. YeW. LiX. ZhangX. LinX. WeiW. HuangX. QianY. ZhuangH. JinJ. LuY. Characterization of the newly established homoharringtonine- (HHT-) resistant cell lines and mechanisms of resistance.J. Oncol.2022202211110.1155/2022/281393836081671
     [Google Scholar]
  58. LiF. YeW. YaoY. WeiW. LinX. ZhuangH. LiC. LiX. LingQ. HuC. HuangX. QianY. MaoS. HuangJ. LuY. JinJ. Spermatogenesis associated serine rich 2 like plays a prognostic factor and therapeutic target in acute myeloid leukemia by regulating the JAK2/STAT3/STAT5 axis.J. Transl. Med.202321111510.1186/s12967‑023‑03968‑036774517
     [Google Scholar]
  59. PlataniasL.C. Map kinase signaling pathways and hematologic malignancies.Blood2003101124667467910.1182/blood‑2002‑12‑364712623839
     [Google Scholar]
  60. YangH.S. MatthewsC.P. ClairT. WangQ. BakerA.R. LiC.C.H. TanT.H. ColburnN.H. Tumorigenesis suppressor Pdcd4 down-regulates mitogen-activated protein kinase kinase kinase kinase 1 expression to suppress colon carcinoma cell invasion.Mol. Cell. Biol.20062641297130610.1128/MCB.26.4.1297‑1306.200616449643
     [Google Scholar]
  61. LingQ. LiF. ZhangX. MaoS. LinX. PanJ. YeW. WeiW. QianY. HuC. HuangX. WangJ. WangH. HuangJ. WangY. JinJ. MAP4K1 functions as a tumor promotor and drug mediator for AML via modulation of DNA damage/repair system and MAPK pathway.EBioMedicine20216910344110.1016/j.ebiom.2021.10344134166980
     [Google Scholar]
  62. ZhangY. LiN. ChangZ. WangH. PeiH. ZhangD. ZhangQ. HuangJ. GuoY. ZhaoY. PanY. ChenC. ChenY. The metabolic signature of AML cells treated with Homoharringtonine.Front. Oncol.20221293152710.3389/fonc.2022.93152735774129
     [Google Scholar]
  63. LiuH. XuR. GaoC. ZhuT. LiuL. YangY. ZengH. HuangY. WangH. Metabolic molecule PLA2G2D is a potential prognostic biomarker correlating with immune cell infiltration and the expression of immune checkpoint genes in cervical squamous cell carcinoma.Front. Oncol.20211175566810.3389/fonc.2021.75566834733790
     [Google Scholar]
  64. DöhnerH. WeiA.H. LöwenbergB. Towards precision medicine for AML.Nat. Rev. Clin. Oncol.202118957759010.1038/s41571‑021‑00509‑w34006997
     [Google Scholar]
  65. FaliniB. NicolettiI. MartelliM.F. MecucciC. Acute myeloid leukemia carrying cytoplasmic/mutated nucleophosmin (NPMc+ AML): Biologic and clinical features.Blood2007109387488510.1182/blood‑2006‑07‑01225217008539
     [Google Scholar]
  66. DuployezN. ChebrekL. HelevautN. FournierE. BembaM. CaillaultA. GeffroyS. PreudhommeC. A novel type of NPM1 mutation characterized by multiple internal tandem repeats in a case of cytogenetically normal acute myeloid leukemia.Haematologica201810312e575e57710.3324/haematol.2018.19095929903763
     [Google Scholar]
  67. XueJ. ChuP. GaoW. WangF. GaoY. LiuS. KangZ. YanJ. WangH. XPO1 is a new target of homoharringtonine (HHT): Making NPMc+ AML cells much more sensitive to HHT treatment.Biochem. Biophys. Res. Commun.202367515516110.1016/j.bbrc.2023.07.02737473530
     [Google Scholar]
  68. LiF. LingQ. LianJ. ChenY. HuC. YangM. ZhangX. LiC. MaoS. YeW. LiX. LinX. WeiW. HuangX. PanJ. QianY. WangJ. LuY. JinJ. Dihydropyrimidinase-like 2 can serve as a novel therapeutic target and prognostic biomarker in acute myeloid leukemia.Cancer Med.20231278319833010.1002/cam4.553136621846
     [Google Scholar]
  69. NouraM. MoritaK. KiyoseH. MatsuoH. Nishinaka-AraiY. KurokawaM. KamikuboY. AdachiS. Pivotal role of DPYSL2A in KLF4-mediated monocytic differentiation of acute myeloid leukemia cells.Sci. Rep.20201012024510.1038/s41598‑020‑76951‑033219287
     [Google Scholar]
  70. RobichaudN. del RinconS.V. HuorB. AlainT. PetruccelliL.A. HearndenJ. GoncalvesC. GrotegutS. SpruckC.H. FuricL. LarssonO. MullerW.J. MillerW.H. SonenbergN. Phosphorylation of eIF4E promotes EMT and metastasis via translational control of SNAIL and MMP-3.Oncogene201534162032204210.1038/onc.2014.14624909168
     [Google Scholar]
  71. ZhouH. XuR.Z. GuY. ShiP.F. QianS. Targeting of phospho-eIF4E by homoharringtonine eradicates a distinct subset of human acute myeloid leukemia.Leuk. Lymphoma20206151084109610.1080/10428194.2017.139022929334312
     [Google Scholar]
  72. YoshimotoG. MiyamotoT. Jabbarzadeh-TabriziS. IinoT. RocnikJ.L. KikushigeY. MoriY. ShimaT. IwasakiH. TakenakaK. NagafujiK. MizunoS. NiiroH. GillilandG.D. AkashiK. FLT3-ITD up-regulates MCL-1 to promote survival of stem cells in acute myeloid leukemia via FLT3-ITD–specific STAT5 activation.Blood2009114245034504310.1182/blood‑2008‑12‑19605519808698
     [Google Scholar]
  73. WestermaierY. BarrilX. ScapozzaL. Virtual screening: An in silico tool for interlacing the chemical universe with the proteome.Methods201571445710.1016/j.ymeth.2014.08.00125193260
     [Google Scholar]
  74. ChenJ. MuQ. LiX. YinX. YuM. JinJ. LiC. ZhouY. ZhouJ. SuoS. LuD. JinJ. Homoharringtonine targets Smad3 and TGF-β pathway to inhibit the proliferation of acute myeloid leukemia cells.Oncotarget2017825403184032610.18632/oncotarget.1695628454099
     [Google Scholar]
  75. GuptaK. GulenF. SunL. AguileraR. ChakrabartiA. KiselarJ. AgarwalM.K. WaldD.N. GSK3 is a regulator of RAR-mediated differentiation.Leukemia20122661277128510.1038/leu.2012.222222598
     [Google Scholar]
  76. WangZ. IwasakiM. FicaraF. LinC. MathenyC. WongS.H.K. SmithK.S. ClearyM.L. GSK-3 promotes conditional association of CREB and its coactivators with MEIS1 to facilitate HOX-mediated transcription and oncogenesis.Cancer Cell201017659760810.1016/j.ccr.2010.04.02420541704
     [Google Scholar]
  77. WangZ. SmithK.S. MurphyM. PilotoO. SomervailleT.C.P. ClearyM.L. Glycogen synthase kinase 3 in MLL leukaemia maintenance and targeted therapy.Nature200845572171205120910.1038/nature0728418806775
     [Google Scholar]
  78. DobleB.W. WoodgettJ.R. GSK-3: Tricks of the trade for a multi-tasking kinase.J. Cell Sci.200311671175118610.1242/jcs.0038412615961
     [Google Scholar]
  79. HoeflichK.P. LuoJ. RubieE.A. TsaoM.S. JinO. WoodgettJ.R. Requirement for glycogen synthase kinase-3β in cell survival and NF-κB activation.Nature20004066791869010.1038/3501757410894547
     [Google Scholar]
  80. NaitoS. BilimV. YuukiK. UgolkovA. MotoyamaT. NagaokaA. KatoT. TomitaY. Glycogen synthase kinase-3beta: A prognostic marker and a potential therapeutic target in human bladder cancer.Clin. Cancer Res.201016215124513210.1158/1078‑0432.CCR‑10‑027520889919
     [Google Scholar]
  81. OugolkovA.V. BoneN.D. Fernandez-ZapicoM.E. KayN.E. BilladeauD.D. Inhibition of glycogen synthase kinase-3 activity leads to epigenetic silencing of nuclear factor κB target genes and induction of apoptosis in chronic lymphocytic leukemia B cells.Blood2007110273574210.1182/blood‑2006‑12‑06094717463171
     [Google Scholar]
  82. ShaoJ. TengY. PadiaR. HongS. NohH. XieX. MummJ.S. DongZ. DingH.F. CowellJ. KimJ. HanJ. HuangS. COP1 and GSK3β cooperate to promote c-Jun degradation and inhibit breast cancer cell tumorigenesis.Neoplasia20131591075IN1110.1593/neo.1396624027432
     [Google Scholar]
/content/journals/cctr/10.2174/0115733947317749240918113844
Loading
A Review Progress on Homoharringtonine’s Effect on Acute Myeloid Leukemia
Curr Cancer Ther Rev 21, 910 (2025); https://doi.org/10.2174/0115733947317749240918113844
/content/journals/cctr/10.2174/0115733947317749240918113844
/content/journals/cctr/10.2174/0115733947317749240918113844
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): AML; combination therapy; HHT; MCL-1; new targets; p-eIF4E; resistance

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test