Skip to content
2000
Volume 25, Issue 7
  • ISSN: 1566-5240
  • E-ISSN: 1875-5666

Abstract

Background

Increased expression of MRP 1 in AML patients results in the efflux of drugs from the cells, preventing the patient from achieving remission or potentially leading to relapse. Several studies have demonstrated that early identification of ABC transporter may yield favorable outcomes.

Aims and objectives

The objectives of the study were to investigate the correlation between MRP 1 gene expression and MRP 1 protein levels and the response to remission induction in AML patients.

Methods

A total of 40 AML patients were recruited from March 2021 to June 2022. Peripheral blood was collected in two tubes (yellow and purple top) to assess the MRP 1 gene and protein. For MRP 1 gene assessment, RNA was isolated from blood samples, cDNA was prepared, and qRT-PCR was performed to analyze gene expression. The relationship between the gene and complete remission was determined. Identification of MRP 1 protein was conducted using ELISA, and the relationship between protein levels and complete remission (CR) was explored.

Results

Most of the patients were aged between 25 and 39 years, encompassing both males and females. This study observed a clinical correlation between MRP 1 gene expression and complete remission. The findings revealed that 69.2 percent of patients with high gene expression failed to achieve complete remission, whereas the analysis of MRP 1 protein in relation to complete remission showed no statistical significance. The MRP1 gene showed high expression (66.7%) in patients with FLT3 mutation, whereas low expression of MRP1 was associated with a high occurrence (60%) of NMP1 mutation.

Conclusion

Further comprehensive multicenter studies with larger sample sizes are required to validate the findings of this study. It is recommended to pinpoint the mechanism and regulation of MRP 1 and its interaction with other molecular pathways.

Loading

Article metrics loading...

/content/journals/cmm/10.2174/0115665240303070240626075757
2024-07-09
2025-10-27
Loading full text...

Full text loading...

References

  1. World Health OrganizationWorld health statistics 2010.2010Available From: https://www.who.int/publications/i/item/9789241563987
    [Google Scholar]
  2. KunadtD. DransfeldC. DillC. Multidrug-related protein 1 (MRP1) polymorphisms rs129081, rs212090, and rs212091 predict survival in normal karyotype acute myeloid leukemia.Ann. Hematol.20209992173218010.1007/s00277‑020‑04163‑7 32621177
    [Google Scholar]
  3. ArberD.A. OraziA. HasserjianR. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia.Blood2016127202391240510.1182/blood‑2016‑03‑643544 27069254
    [Google Scholar]
  4. BoutinL. ArnautouP. TrignolA. Mesenchymal stromal cells confer chemoresistance to myeloid leukemia blasts through Side Population functionality and ABC transporter activation.Haematologica20201054987999810.3324/haematol.2018.214379 31289201
    [Google Scholar]
  5. Megías-VericatJ.E. Martínez-CuadrónD. HerreroM.J. Impact of combinations of single-nucleotide polymorphisms of anthracycline transporter genes upon the efficacy and toxicity of induction chemotherapy in acute myeloid leukemia.Leuk. Lymphoma202162365966810.1080/10428194.2020.1839650 33135528
    [Google Scholar]
  6. JohnsonZ.L. ChenJ. ATP binding enables substrate release from multidrug resistance protein 1.Cell20181721-2818910.1016/j.cell.2017.12.005
    [Google Scholar]
  7. ChenB. LeeJ.B. KangH. MindenM.D. ZhangL. Targeting chemotherapy-resistant leukemia by combining DNT cellular therapy with conventional chemotherapy.J. Exp. Clin. Cancer Res.20183718810.1186/s13046‑018‑0756‑9 29690909
    [Google Scholar]
  8. PaprockaM. Bielawska-PohlA. RossowskaJ. MRP1 protein expression in leukemic stem cells as a negative prognostic marker in acute myeloid leukemia patients.Eur. J. Haematol.201799541542210.1111/ejh.12938 28805931
    [Google Scholar]
  9. ZhangJ. GuY. ChenB. Mechanisms of drug resistance in acute myeloid leukemia.OncoTargets Ther.2019121937194510.2147/OTT.S191621 30881045
    [Google Scholar]
  10. KulsoomB. ShamsiT.S. AfsarN.A. Lung resistance-related protein (LRP) predicts favorable therapeutic outcome in Acute Myeloid Leukemia.Sci. Rep.20199137810.1038/s41598‑018‑36780‑8 30674943
    [Google Scholar]
  11. EmmanouilidiA. CasariI. Gokcen AkkayaB. Inhibition of the lysophosphatidylinositol transporter ABCC1 reduces prostate cancer cell growth and sensitizes to chemotherapy.Cancers2020128202210.3390/cancers12082022 32718079
    [Google Scholar]
  12. MuriithiW. Wanjiku MachariaL. Pilotto HemingC. ABC transporters and the hallmarks of cancer: Roles in cancer aggressiveness beyond multidrug resistance.Cancer Biol. Med.202017225326910.20892/j.issn.2095‑3941.2019.0284 32587767
    [Google Scholar]
  13. VasconcelosF.C. de SouzaP.S. HancioT. de FariaF.C.C. MaiaR.C. Update on drug transporter proteins in acute myeloid leukemia: Pathological implication and clinical setting.Crit. Rev. Oncol. Hematol.202116010328110.1016/j.critrevonc.2021.103281 33667660
    [Google Scholar]
  14. LiuB. LiL.J. GongX. ZhangW. ZhangH. ZhaoL. Co-expression of ATP binding cassette transporters is associated with poor prognosis in acute myeloid leukemia.Oncol. Lett.20181556671667710.3892/ol.2018.8095 29616130
    [Google Scholar]
  15. BartholomaeS. GruhnB. DebatinK.M. Coexpression of multiple ABC‐transporters is strongly associated with treatment response in childhood acute myeloid leukemia.Pediatr. Blood Cancer201663224224710.1002/pbc.25785 26512967
    [Google Scholar]
  16. RobeyR.W. PluchinoK.M. HallM.D. FojoA.T. BatesS.E. GottesmanM.M. Revisiting the role of ABC transporters in multidrug-resistant cancer.Nat. Rev. Cancer201818745246410.1038/s41568‑018‑0005‑8 29643473
    [Google Scholar]
  17. DamianiD. TiribelliM. RaspadoriD. The role of MDR‐related proteins in the prognosis of adult acute myeloid leukaemia (AML) with normal karyotype.Hematol. Oncol.2007251384310.1002/hon.806 17200981
    [Google Scholar]
  18. MichieliM. DamianiD. ErmacoraA. P‐glycoprotein, lung resistance‐related protein and multidrug resistance associated protein in de novo acute non‐lymphocytic leukaemias: Biological and clinical implications.Br. J. Haematol.1999104232833510.1046/j.1365‑2141.1999.01172.x 10050716
    [Google Scholar]
  19. VakitiA. MewawallaP. Acute Myeloid Leukemia.Treasure Island, FLStatPearls2020
    [Google Scholar]
  20. LiB. TangH. ChengZ. ZhangY. XiangH. The current situation and future trend of leukemia mortality by sex and area in China.Front. Public Health2020859821510.3389/fpubh.2020.598215 33363091
    [Google Scholar]
  21. EsteyE. KantarjianH. KeatingM. Therapy for acute myeloid leukemia. Hematology: Basic Principles and Practice. 4th edPhiladelphiaElsevier200510991120
    [Google Scholar]
  22. ReesJ. GrayR.G. SwirskyD. HayhoeF.G. Principal results of the medical research council’s 8th acute myeloid leukaemia trial.Lancet198632885181236124110.1016/S0140‑6736(86)92674‑7 2878130
    [Google Scholar]
  23. LeithC.P. KopeckyK.J. ChenI.M. Frequency and clinical significance of the expression of the multidrug resistance proteins MDR1/P-glycoprotein, MRP1, and LRP in acute myeloid leukemia: A Southwest Oncology Group Study.Blood199994310861099 10419902
    [Google Scholar]
  24. LegrandO. SimoninG. Beauchamp-NicoudA. ZittounR. MarieJ.P. Simultaneous activity of MRP1 and Pgp is correlated with in vitro resistance to daunorubicin and with in vivo resistance in adult acute myeloid leukemia.Blood19999431046105610.1182/blood.V94.3.1046.415k03_1046_1056 10419897
    [Google Scholar]
  25. van den Heuvel-EibrinkM.M. van der HoltB. BurnettA.K. CD34-related coexpression of MDR1 and BCRP indicates a clinically resistant phenotype in patients with acute myeloid leukemia (AML) of older age.Ann. Hematol.200786532933710.1007/s00277‑007‑0269‑7 17340137
    [Google Scholar]
  26. EbeedS.A. SadekN.A. ZaherE.R. MahmoudM.M. NabilG. ElbenhawyS.A. Role of MRP-1 and GST-Pi in MDR and their inhibition by indomethacin in AML.Alex. J. Med.201753325125910.1016/j.ajme.2016.04.002
    [Google Scholar]
  27. FilipitsM. StranzlT. PohlG. Drug resistance factors in acute myeloid leukemia: A comparative analysis.Leukemia2000141687610.1038/sj.leu.2401634 10637479
    [Google Scholar]
  28. AltenbergG. Structure of multidrug-resistance proteins of the ATP-binding cassette (ABC) superfamily.Curr. Med. Chem. Anticancer Agents200441536210.2174/1568011043482160 14754412
    [Google Scholar]
  29. SalviaA.M. CuvielloF. ColuzziS. Expression of some ATP-binding cassette transporters in acute myeloid leukemia.Hematol. Rep.201794740610.4081/hr.2017.7406 29333226
    [Google Scholar]
  30. LegrandO. PerrotJ.Y. SimoninG. Adult biphenotypic acute leukaemia: An entity with poor prognosis which is related to unfavourable cytogenetics and P‐glycoprotein over‐expression.Br. J. Haematol.1998100114715510.1046/j.1365‑2141.1998.00523.x 9450804
    [Google Scholar]
  31. MahjoubiF. GolalipourM. GhavamzadehA. AlimoghaddamK. Expression of MRP1 gene in acute leukemia.Sao Paulo Med. J.2008126317217910.1590/S1516‑31802008000300007 18711657
    [Google Scholar]
  32. KolesnikovaM. Sen’kovaA. TairovaS. OvchinnikovV. PospelovaT. ZenkovaM. Clinical and prognostic significance of cell sensitivity to chemotherapy detected in vitro on treatment response and survival of leukemia patients.J. Pers. Med.2019922410.3390/jpm9020024 31067780
    [Google Scholar]
  33. AbelB. MurakamiM. ToshD.K. Interaction of A3 adenosine receptor ligands with the human multidrug transporter ABCG2.Eur. J. Med. Chem.202223111410310.1016/j.ejmech.2022.114103 35152062
    [Google Scholar]
  34. HuangY. HuJ. LuT. Acute myeloid leukemia patient with FLT3-ITD and NPM1 double mutation should undergo allogeneic hematopoietic stem cell transplantation in CR1 for better prognosis.Cancer Manag. Res.2019114129414210.2147/CMAR.S194523 31190985
    [Google Scholar]
  35. BodduP.C. KadiaT.M. Garcia-ManeroG. Validation of the 2017 European LeukemiaNet classification for acute myeloid leukemia with NPM1 and FLT3 ‐internal tandem duplication genotypes.Cancer201912571091110010.1002/cncr.31885 30521114
    [Google Scholar]
  36. HaradaY. NagataY. KiharaR. Prognostic analysis according to the 2017 ELN risk stratification by genetics in adult acute myeloid leukemia patients treated in the Japan Adult Leukemia Study Group (JALSG) AML201 study.Leuk. Res.201866202710.1016/j.leukres.2018.01.008 29360622
    [Google Scholar]
  37. LiuS.B. QiuQ.C. BaoX.B. Pattern and prognostic value ofFLT 3 ‐ ITD mutations in Chinese de novo adult acute myeloid leukemia.Cancer Sci.2018109123981399210.1111/cas.13835 30320942
    [Google Scholar]
  38. HirschP. TangR. MarzacC. Prognostic impact of high ABC transporter activity in 111 adult acute myeloid leukemia patients with normal cytogenetics when compared to FLT3, NPM1, CEBPA and BAALC.Haematologica201297224124510.3324/haematol.2010.034447 22058196
    [Google Scholar]
  39. KeramatiM.R. Correlation of BCRP expression to NPM1 mutations in acute myeloid Leukemia.Uluslar Hematol Onkol Derg201828318018610.4999/uhod.182715
    [Google Scholar]
  40. KussB.J. EyreH.J. LaneS.A. Deletion of gene for multidrug resistance in acute myeloid leukaemia with inversion in chromosome 16: Prognostic implications.Lancet199434389121531153410.1016/S0140‑6736(94)92938‑6 7911871
    [Google Scholar]
/content/journals/cmm/10.2174/0115665240303070240626075757
Loading
/content/journals/cmm/10.2174/0115665240303070240626075757
Loading

Data & Media loading...


  • Article Type:
    Research Article
Keyword(s): cytogenetics; FLT 3; MRP1; myeloid leukemia; NPM 1; remission
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